New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout
<p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been impl...
Ausführliche Beschreibung
Autor*in: |
Hileman Stanley M [verfasserIn] Werner David F [verfasserIn] Hardy Steven L [verfasserIn] Ferguson Carolyn [verfasserIn] DeLorey Timothy M [verfasserIn] Homanics Gregg E [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2007 |
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Übergeordnetes Werk: |
In: BMC Neuroscience - BMC, 2003, 8(2007), 1, p 85 |
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Übergeordnetes Werk: |
volume:8 ; year:2007 ; number:1, p 85 |
Links: |
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DOI / URN: |
10.1186/1471-2202-8-85 |
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Katalog-ID: |
DOAJ042065003 |
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520 | |a <p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< | ||
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10.1186/1471-2202-8-85 doi (DE-627)DOAJ042065003 (DE-599)DOAJ8c670e3e8ca84a93976fec6b1c323182 DE-627 ger DE-627 rakwb eng RC321-571 QP351-495 Hileman Stanley M verfasserin aut New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< Neurosciences. Biological psychiatry. Neuropsychiatry Neurophysiology and neuropsychology Werner David F verfasserin aut Hardy Steven L verfasserin aut Ferguson Carolyn verfasserin aut DeLorey Timothy M verfasserin aut Homanics Gregg E verfasserin aut In BMC Neuroscience BMC, 2003 8(2007), 1, p 85 (DE-627)326643648 (DE-600)2041344-0 14712202 nnns volume:8 year:2007 number:1, p 85 https://doi.org/10.1186/1471-2202-8-85 kostenfrei https://doaj.org/article/8c670e3e8ca84a93976fec6b1c323182 kostenfrei http://www.biomedcentral.com/1471-2202/8/85 kostenfrei https://doaj.org/toc/1471-2202 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 1, p 85 |
spelling |
10.1186/1471-2202-8-85 doi (DE-627)DOAJ042065003 (DE-599)DOAJ8c670e3e8ca84a93976fec6b1c323182 DE-627 ger DE-627 rakwb eng RC321-571 QP351-495 Hileman Stanley M verfasserin aut New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< Neurosciences. Biological psychiatry. Neuropsychiatry Neurophysiology and neuropsychology Werner David F verfasserin aut Hardy Steven L verfasserin aut Ferguson Carolyn verfasserin aut DeLorey Timothy M verfasserin aut Homanics Gregg E verfasserin aut In BMC Neuroscience BMC, 2003 8(2007), 1, p 85 (DE-627)326643648 (DE-600)2041344-0 14712202 nnns volume:8 year:2007 number:1, p 85 https://doi.org/10.1186/1471-2202-8-85 kostenfrei https://doaj.org/article/8c670e3e8ca84a93976fec6b1c323182 kostenfrei http://www.biomedcentral.com/1471-2202/8/85 kostenfrei https://doaj.org/toc/1471-2202 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 1, p 85 |
allfields_unstemmed |
10.1186/1471-2202-8-85 doi (DE-627)DOAJ042065003 (DE-599)DOAJ8c670e3e8ca84a93976fec6b1c323182 DE-627 ger DE-627 rakwb eng RC321-571 QP351-495 Hileman Stanley M verfasserin aut New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< Neurosciences. Biological psychiatry. Neuropsychiatry Neurophysiology and neuropsychology Werner David F verfasserin aut Hardy Steven L verfasserin aut Ferguson Carolyn verfasserin aut DeLorey Timothy M verfasserin aut Homanics Gregg E verfasserin aut In BMC Neuroscience BMC, 2003 8(2007), 1, p 85 (DE-627)326643648 (DE-600)2041344-0 14712202 nnns volume:8 year:2007 number:1, p 85 https://doi.org/10.1186/1471-2202-8-85 kostenfrei https://doaj.org/article/8c670e3e8ca84a93976fec6b1c323182 kostenfrei http://www.biomedcentral.com/1471-2202/8/85 kostenfrei https://doaj.org/toc/1471-2202 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 1, p 85 |
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10.1186/1471-2202-8-85 doi (DE-627)DOAJ042065003 (DE-599)DOAJ8c670e3e8ca84a93976fec6b1c323182 DE-627 ger DE-627 rakwb eng RC321-571 QP351-495 Hileman Stanley M verfasserin aut New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< Neurosciences. Biological psychiatry. Neuropsychiatry Neurophysiology and neuropsychology Werner David F verfasserin aut Hardy Steven L verfasserin aut Ferguson Carolyn verfasserin aut DeLorey Timothy M verfasserin aut Homanics Gregg E verfasserin aut In BMC Neuroscience BMC, 2003 8(2007), 1, p 85 (DE-627)326643648 (DE-600)2041344-0 14712202 nnns volume:8 year:2007 number:1, p 85 https://doi.org/10.1186/1471-2202-8-85 kostenfrei https://doaj.org/article/8c670e3e8ca84a93976fec6b1c323182 kostenfrei http://www.biomedcentral.com/1471-2202/8/85 kostenfrei https://doaj.org/toc/1471-2202 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 1, p 85 |
allfieldsSound |
10.1186/1471-2202-8-85 doi (DE-627)DOAJ042065003 (DE-599)DOAJ8c670e3e8ca84a93976fec6b1c323182 DE-627 ger DE-627 rakwb eng RC321-571 QP351-495 Hileman Stanley M verfasserin aut New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< Neurosciences. Biological psychiatry. Neuropsychiatry Neurophysiology and neuropsychology Werner David F verfasserin aut Hardy Steven L verfasserin aut Ferguson Carolyn verfasserin aut DeLorey Timothy M verfasserin aut Homanics Gregg E verfasserin aut In BMC Neuroscience BMC, 2003 8(2007), 1, p 85 (DE-627)326643648 (DE-600)2041344-0 14712202 nnns volume:8 year:2007 number:1, p 85 https://doi.org/10.1186/1471-2202-8-85 kostenfrei https://doaj.org/article/8c670e3e8ca84a93976fec6b1c323182 kostenfrei http://www.biomedcentral.com/1471-2202/8/85 kostenfrei https://doaj.org/toc/1471-2202 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 1, p 85 |
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Hileman Stanley M misc RC321-571 misc QP351-495 misc Neurosciences. Biological psychiatry. Neuropsychiatry misc Neurophysiology and neuropsychology New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout |
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RC321-571 QP351-495 New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout |
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New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout |
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new insight into the role of the β3 subunit of the gaba<sub<a</sub<-r in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout |
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New insight into the role of the β3 subunit of the GABA<sub<A</sub<-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout |
abstract |
<p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< |
abstractGer |
<p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< |
abstract_unstemmed |
<p<Abstract</p< <p<Background</p< <p<The β3 subunit of the γ-aminobutyric acid type A receptor (GABA<sub<A</sub<-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p< <p<Results</p< <p<Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p< <p<Conclusion</p< <p<Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA<sub<A</sub<-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p< |
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7.3995285 |