Screening for Stress Resistance Mutations in the Mouse

Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a hi...
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Autor*in:	Wallace S Chick [verfasserIn] Michael eLudwig [verfasserIn] Xiaoyun eZhao [verfasserIn] David eKitzenberg [verfasserIn] Kristina eWilliams [verfasserIn] Thomas E Johnson [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon

Übergeordnetes Werk:	In: Frontiers in Genetics - Frontiers Media S.A., 2011, 5(2014)
Übergeordnetes Werk:	volume:5 ; year:2014

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fgene.2014.00310

Katalog-ID:	DOAJ021362734

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520			\|a Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies.
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allfields	10.3389/fgene.2014.00310 doi (DE-627)DOAJ021362734 (DE-599)DOAJ2426aaacf13741c89e0d0bdc80fa355c DE-627 ger DE-627 rakwb eng QH426-470 Wallace S Chick verfasserin aut Screening for Stress Resistance Mutations in the Mouse 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies. Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon Genetics Michael eLudwig verfasserin aut Xiaoyun eZhao verfasserin aut David eKitzenberg verfasserin aut Kristina eWilliams verfasserin aut Thomas E Johnson verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 5(2014) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:5 year:2014 https://doi.org/10.3389/fgene.2014.00310 kostenfrei https://doaj.org/article/2426aaacf13741c89e0d0bdc80fa355c kostenfrei http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00310/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 5 2014
spelling	10.3389/fgene.2014.00310 doi (DE-627)DOAJ021362734 (DE-599)DOAJ2426aaacf13741c89e0d0bdc80fa355c DE-627 ger DE-627 rakwb eng QH426-470 Wallace S Chick verfasserin aut Screening for Stress Resistance Mutations in the Mouse 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies. Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon Genetics Michael eLudwig verfasserin aut Xiaoyun eZhao verfasserin aut David eKitzenberg verfasserin aut Kristina eWilliams verfasserin aut Thomas E Johnson verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 5(2014) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:5 year:2014 https://doi.org/10.3389/fgene.2014.00310 kostenfrei https://doaj.org/article/2426aaacf13741c89e0d0bdc80fa355c kostenfrei http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00310/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 5 2014
allfields_unstemmed	10.3389/fgene.2014.00310 doi (DE-627)DOAJ021362734 (DE-599)DOAJ2426aaacf13741c89e0d0bdc80fa355c DE-627 ger DE-627 rakwb eng QH426-470 Wallace S Chick verfasserin aut Screening for Stress Resistance Mutations in the Mouse 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies. Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon Genetics Michael eLudwig verfasserin aut Xiaoyun eZhao verfasserin aut David eKitzenberg verfasserin aut Kristina eWilliams verfasserin aut Thomas E Johnson verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 5(2014) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:5 year:2014 https://doi.org/10.3389/fgene.2014.00310 kostenfrei https://doaj.org/article/2426aaacf13741c89e0d0bdc80fa355c kostenfrei http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00310/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 5 2014
allfieldsGer	10.3389/fgene.2014.00310 doi (DE-627)DOAJ021362734 (DE-599)DOAJ2426aaacf13741c89e0d0bdc80fa355c DE-627 ger DE-627 rakwb eng QH426-470 Wallace S Chick verfasserin aut Screening for Stress Resistance Mutations in the Mouse 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies. Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon Genetics Michael eLudwig verfasserin aut Xiaoyun eZhao verfasserin aut David eKitzenberg verfasserin aut Kristina eWilliams verfasserin aut Thomas E Johnson verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 5(2014) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:5 year:2014 https://doi.org/10.3389/fgene.2014.00310 kostenfrei https://doaj.org/article/2426aaacf13741c89e0d0bdc80fa355c kostenfrei http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00310/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 5 2014
allfieldsSound	10.3389/fgene.2014.00310 doi (DE-627)DOAJ021362734 (DE-599)DOAJ2426aaacf13741c89e0d0bdc80fa355c DE-627 ger DE-627 rakwb eng QH426-470 Wallace S Chick verfasserin aut Screening for Stress Resistance Mutations in the Mouse 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies. Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon Genetics Michael eLudwig verfasserin aut Xiaoyun eZhao verfasserin aut David eKitzenberg verfasserin aut Kristina eWilliams verfasserin aut Thomas E Johnson verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 5(2014) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:5 year:2014 https://doi.org/10.3389/fgene.2014.00310 kostenfrei https://doaj.org/article/2426aaacf13741c89e0d0bdc80fa355c kostenfrei http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00310/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 5 2014
language	English
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topic_facet	Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon Genetics
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container_title	Frontiers in Genetics
authorswithroles_txt_mv	Wallace S Chick @@aut@@ Michael eLudwig @@aut@@ Xiaoyun eZhao @@aut@@ David eKitzenberg @@aut@@ Kristina eWilliams @@aut@@ Thomas E Johnson @@aut@@
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callnumber-first	Q - Science
author	Wallace S Chick
spellingShingle	Wallace S Chick misc QH426-470 misc Embryonic Stem Cells misc Mice misc Paraquat misc Forward genetics misc Stress resistance misc piggyBac transposon misc Genetics Screening for Stress Resistance Mutations in the Mouse
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topic_title	QH426-470 Screening for Stress Resistance Mutations in the Mouse Embryonic Stem Cells Mice Paraquat Forward genetics Stress resistance piggyBac transposon
topic	misc QH426-470 misc Embryonic Stem Cells misc Mice misc Paraquat misc Forward genetics misc Stress resistance misc piggyBac transposon misc Genetics
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title	Screening for Stress Resistance Mutations in the Mouse
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title_full	Screening for Stress Resistance Mutations in the Mouse
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title_sort	screening for stress resistance mutations in the mouse
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title_auth	Screening for Stress Resistance Mutations in the Mouse
abstract	Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies.
abstractGer	Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies.
abstract_unstemmed	Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress-resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies.
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title_short	Screening for Stress Resistance Mutations in the Mouse
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