Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains
In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Wickert, L. [verfasserIn] Selbig, J. [verfasserIn] Watzka, M. [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|
| Erschienen: |
Oxford, UK: Blackwell Science Ltd ; 2000 |
|---|
| Schlagwörter: |
|---|
| Umfang: |
Online-Ressource |
|---|
| Reproduktion: |
2008 ; Blackwell Publishing Journal Backfiles 1879-2005 |
|---|---|
| Übergeordnetes Werk: |
In: Journal of neuroendocrinology - Oxford [u.a.] : Wiley-Blackwell, 1989, 12(2000), 9, Seite 0 |
| Übergeordnetes Werk: |
volume:12 ; year:2000 ; number:9 ; pages:0 |
| Links: |
|---|
| DOI / URN: |
10.1046/j.1365-2826.2000.00535.x |
|---|
| Katalog-ID: |
NLEJ243106602 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLEJ243106602 | ||
| 003 | DE-627 | ||
| 005 | 20210707172556.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 120427s2000 xx |||||o 00| ||und c | ||
| 024 | 7 | |a 10.1046/j.1365-2826.2000.00535.x |2 doi | |
| 035 | |a (DE-627)NLEJ243106602 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 100 | 1 | |a Wickert, L. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains |
| 264 | 1 | |a Oxford, UK |b Blackwell Science Ltd |c 2000 | |
| 300 | |a Online-Ressource | ||
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. | ||
| 533 | |d 2008 |f Blackwell Publishing Journal Backfiles 1879-2005 |7 |2008|||||||||| | ||
| 650 | 4 | |a brain tissue | |
| 700 | 1 | |a Selbig, J. |e verfasserin |4 aut | |
| 700 | 1 | |a Watzka, M. |e verfasserin |4 aut | |
| 700 | 1 | |a Stoffel-Wagner, B. |4 oth | |
| 700 | 1 | |a Schramm, J. |4 oth | |
| 700 | 1 | |a Bidlingmeier, F. |4 oth | |
| 700 | 1 | |a Ludwig, M. |4 oth | |
| 773 | 0 | 8 | |i In |t Journal of neuroendocrinology |d Oxford [u.a.] : Wiley-Blackwell, 1989 |g 12(2000), 9, Seite 0 |h Online-Ressource |w (DE-627)NLEJ243926375 |w (DE-600)2007386-0 |x 1365-2826 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2000 |g number:9 |g pages:0 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x |q text/html |x Verlag |z Deutschlandweit zugänglich |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a ZDB-1-DJB | ||
| 912 | |a GBV_NL_ARTICLE | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2000 |e 9 |h 0 | ||
| author_variant |
l w lw j s js m w mw |
|---|---|
| matchkey_str |
article:13652826:2000----::ifrnilraxrsinfhtoieaootcircposlcvratwtiteuabantutraa |
| hierarchy_sort_str |
2000 |
| publishDate |
2000 |
| allfields |
10.1046/j.1365-2826.2000.00535.x doi (DE-627)NLEJ243106602 DE-627 ger DE-627 rakwb Wickert, L. verfasserin aut Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains Oxford, UK Blackwell Science Ltd 2000 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. 2008 Blackwell Publishing Journal Backfiles 1879-2005 |2008|||||||||| brain tissue Selbig, J. verfasserin aut Watzka, M. verfasserin aut Stoffel-Wagner, B. oth Schramm, J. oth Bidlingmeier, F. oth Ludwig, M. oth In Journal of neuroendocrinology Oxford [u.a.] : Wiley-Blackwell, 1989 12(2000), 9, Seite 0 Online-Ressource (DE-627)NLEJ243926375 (DE-600)2007386-0 1365-2826 nnns volume:12 year:2000 number:9 pages:0 http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 12 2000 9 0 |
| spelling |
10.1046/j.1365-2826.2000.00535.x doi (DE-627)NLEJ243106602 DE-627 ger DE-627 rakwb Wickert, L. verfasserin aut Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains Oxford, UK Blackwell Science Ltd 2000 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. 2008 Blackwell Publishing Journal Backfiles 1879-2005 |2008|||||||||| brain tissue Selbig, J. verfasserin aut Watzka, M. verfasserin aut Stoffel-Wagner, B. oth Schramm, J. oth Bidlingmeier, F. oth Ludwig, M. oth In Journal of neuroendocrinology Oxford [u.a.] : Wiley-Blackwell, 1989 12(2000), 9, Seite 0 Online-Ressource (DE-627)NLEJ243926375 (DE-600)2007386-0 1365-2826 nnns volume:12 year:2000 number:9 pages:0 http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 12 2000 9 0 |
| allfields_unstemmed |
10.1046/j.1365-2826.2000.00535.x doi (DE-627)NLEJ243106602 DE-627 ger DE-627 rakwb Wickert, L. verfasserin aut Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains Oxford, UK Blackwell Science Ltd 2000 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. 2008 Blackwell Publishing Journal Backfiles 1879-2005 |2008|||||||||| brain tissue Selbig, J. verfasserin aut Watzka, M. verfasserin aut Stoffel-Wagner, B. oth Schramm, J. oth Bidlingmeier, F. oth Ludwig, M. oth In Journal of neuroendocrinology Oxford [u.a.] : Wiley-Blackwell, 1989 12(2000), 9, Seite 0 Online-Ressource (DE-627)NLEJ243926375 (DE-600)2007386-0 1365-2826 nnns volume:12 year:2000 number:9 pages:0 http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 12 2000 9 0 |
| allfieldsGer |
10.1046/j.1365-2826.2000.00535.x doi (DE-627)NLEJ243106602 DE-627 ger DE-627 rakwb Wickert, L. verfasserin aut Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains Oxford, UK Blackwell Science Ltd 2000 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. 2008 Blackwell Publishing Journal Backfiles 1879-2005 |2008|||||||||| brain tissue Selbig, J. verfasserin aut Watzka, M. verfasserin aut Stoffel-Wagner, B. oth Schramm, J. oth Bidlingmeier, F. oth Ludwig, M. oth In Journal of neuroendocrinology Oxford [u.a.] : Wiley-Blackwell, 1989 12(2000), 9, Seite 0 Online-Ressource (DE-627)NLEJ243926375 (DE-600)2007386-0 1365-2826 nnns volume:12 year:2000 number:9 pages:0 http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 12 2000 9 0 |
| allfieldsSound |
10.1046/j.1365-2826.2000.00535.x doi (DE-627)NLEJ243106602 DE-627 ger DE-627 rakwb Wickert, L. verfasserin aut Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains Oxford, UK Blackwell Science Ltd 2000 Online-Ressource nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. 2008 Blackwell Publishing Journal Backfiles 1879-2005 |2008|||||||||| brain tissue Selbig, J. verfasserin aut Watzka, M. verfasserin aut Stoffel-Wagner, B. oth Schramm, J. oth Bidlingmeier, F. oth Ludwig, M. oth In Journal of neuroendocrinology Oxford [u.a.] : Wiley-Blackwell, 1989 12(2000), 9, Seite 0 Online-Ressource (DE-627)NLEJ243926375 (DE-600)2007386-0 1365-2826 nnns volume:12 year:2000 number:9 pages:0 http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x text/html Verlag Deutschlandweit zugänglich Volltext GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE AR 12 2000 9 0 |
| source |
In Journal of neuroendocrinology 12(2000), 9, Seite 0 volume:12 year:2000 number:9 pages:0 |
| sourceStr |
In Journal of neuroendocrinology 12(2000), 9, Seite 0 volume:12 year:2000 number:9 pages:0 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
brain tissue |
| isfreeaccess_bool |
false |
| container_title |
Journal of neuroendocrinology |
| authorswithroles_txt_mv |
Wickert, L. @@aut@@ Selbig, J. @@aut@@ Watzka, M. @@aut@@ Stoffel-Wagner, B. @@oth@@ Schramm, J. @@oth@@ Bidlingmeier, F. @@oth@@ Ludwig, M. @@oth@@ |
| publishDateDaySort_date |
2000-01-01T00:00:00Z |
| hierarchy_top_id |
NLEJ243926375 |
| id |
NLEJ243106602 |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ243106602</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20210707172556.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">120427s2000 xx |||||o 00| ||und c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1046/j.1365-2826.2000.00535.x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ243106602</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Wickert, L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Oxford, UK</subfield><subfield code="b">Blackwell Science Ltd</subfield><subfield code="c">2000</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event.</subfield></datafield><datafield tag="533" ind1=" " ind2=" "><subfield code="d">2008</subfield><subfield code="f">Blackwell Publishing Journal Backfiles 1879-2005</subfield><subfield code="7">|2008||||||||||</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">brain tissue</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Selbig, J.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Watzka, M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Stoffel-Wagner, B.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Schramm, J.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bidlingmeier, F.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ludwig, M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Journal of neuroendocrinology</subfield><subfield code="d">Oxford [u.a.] : Wiley-Blackwell, 1989</subfield><subfield code="g">12(2000), 9, Seite 0</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)NLEJ243926375</subfield><subfield code="w">(DE-600)2007386-0</subfield><subfield code="x">1365-2826</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:12</subfield><subfield code="g">year:2000</subfield><subfield code="g">number:9</subfield><subfield code="g">pages:0</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x</subfield><subfield code="q">text/html</subfield><subfield code="x">Verlag</subfield><subfield code="z">Deutschlandweit zugänglich</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ZDB-1-DJB</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_NL_ARTICLE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">12</subfield><subfield code="j">2000</subfield><subfield code="e">9</subfield><subfield code="h">0</subfield></datafield></record></collection>
|
| series2 |
Blackwell Publishing Journal Backfiles 1879-2005 |
| author |
Wickert, L. |
| spellingShingle |
Wickert, L. misc brain tissue Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains |
| authorStr |
Wickert, L. |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)NLEJ243926375 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| author_role |
aut aut aut |
| collection |
NL |
| publishPlace |
Oxford, UK |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
1365-2826 |
| topic_title |
Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains brain tissue |
| publisher |
Blackwell Science Ltd |
| publisherStr |
Blackwell Science Ltd |
| topic |
misc brain tissue |
| topic_unstemmed |
misc brain tissue |
| topic_browse |
misc brain tissue |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
b s w bsw j s js f b fb m l ml |
| hierarchy_parent_title |
Journal of neuroendocrinology |
| hierarchy_parent_id |
NLEJ243926375 |
| hierarchy_top_title |
Journal of neuroendocrinology |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)NLEJ243926375 (DE-600)2007386-0 |
| title |
Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains |
| ctrlnum |
(DE-627)NLEJ243106602 |
| title_full |
Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains |
| author_sort |
Wickert, L. |
| journal |
Journal of neuroendocrinology |
| journalStr |
Journal of neuroendocrinology |
| isOA_bool |
false |
| recordtype |
marc |
| publishDateSort |
2000 |
| contenttype_str_mv |
zzz |
| container_start_page |
0 |
| author_browse |
Wickert, L. Selbig, J. Watzka, M. |
| container_volume |
12 |
| physical |
Online-Ressource |
| format_se |
Elektronische Aufsätze |
| author-letter |
Wickert, L. |
| doi_str_mv |
10.1046/j.1365-2826.2000.00535.x |
| author2-role |
verfasserin |
| title_sort |
differential mrna expression of the two mineralocorticoid receptor splice variants within the human brain: structure analysis of their different dna binding domains |
| title_auth |
Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains |
| abstract |
In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. |
| abstractGer |
In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. |
| abstract_unstemmed |
In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event. |
| collection_details |
GBV_USEFLAG_U ZDB-1-DJB GBV_NL_ARTICLE |
| container_issue |
9 |
| title_short |
Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains |
| url |
http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x |
| remote_bool |
true |
| author2 |
Selbig, J. Watzka, M. Stoffel-Wagner, B. Schramm, J. Bidlingmeier, F. Ludwig, M. |
| author2Str |
Selbig, J. Watzka, M. Stoffel-Wagner, B. Schramm, J. Bidlingmeier, F. Ludwig, M. |
| ppnlink |
NLEJ243926375 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth |
| doi_str |
10.1046/j.1365-2826.2000.00535.x |
| up_date |
2024-07-06T04:18:01.823Z |
| _version_ |
1803801834889936896 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ243106602</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20210707172556.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">120427s2000 xx |||||o 00| ||und c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1046/j.1365-2826.2000.00535.x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ243106602</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Wickert, L.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Differential mRNA Expression of the Two Mineralocorticoid Receptor Splice Variants Within the Human Brain: Structure Analysis of their Different DNA Binding Domains</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Oxford, UK</subfield><subfield code="b">Blackwell Science Ltd</subfield><subfield code="c">2000</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but signi®cant difference of the MR+4 mRNA splice variant proportions in cortex (9.5t0.8%) and subcortical white matter (6.6t0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue speci®c alternative splicing of the MR mRNA. The frequent occurence of the MR+4 transcript raises the question of its functional signi®cance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc ®ngers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event.</subfield></datafield><datafield tag="533" ind1=" " ind2=" "><subfield code="d">2008</subfield><subfield code="f">Blackwell Publishing Journal Backfiles 1879-2005</subfield><subfield code="7">|2008||||||||||</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">brain tissue</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Selbig, J.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Watzka, M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Stoffel-Wagner, B.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Schramm, J.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bidlingmeier, F.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ludwig, M.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Journal of neuroendocrinology</subfield><subfield code="d">Oxford [u.a.] : Wiley-Blackwell, 1989</subfield><subfield code="g">12(2000), 9, Seite 0</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)NLEJ243926375</subfield><subfield code="w">(DE-600)2007386-0</subfield><subfield code="x">1365-2826</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:12</subfield><subfield code="g">year:2000</subfield><subfield code="g">number:9</subfield><subfield code="g">pages:0</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://dx.doi.org/10.1046/j.1365-2826.2000.00535.x</subfield><subfield code="q">text/html</subfield><subfield code="x">Verlag</subfield><subfield code="z">Deutschlandweit zugänglich</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ZDB-1-DJB</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_NL_ARTICLE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">12</subfield><subfield code="j">2000</subfield><subfield code="e">9</subfield><subfield code="h">0</subfield></datafield></record></collection>
|
| score |
7.3996487 |