Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review
Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest that several endurance-associated traits are ≈50% inherited. However, we still poorly understand what DNA sequence variants contri...
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doaj-a066ad716ba7445d9a0a081a59f21ca92020-11-25T00:13:55ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-03-011010.3389/fphys.2019.00262440662Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature ReviewFakhreddin Yaghoob Nezhad0Sander A. J. Verbrugge1Martin Schönfelder2Lore Becker3Martin Hrabě de Angelis4Martin Hrabě de Angelis5Martin Hrabě de Angelis6Henning Wackerhage7Exercise Biology Group, Department of Sport and Health Sciences, Technical University of Munich, Munich, GermanyExercise Biology Group, Department of Sport and Health Sciences, Technical University of Munich, Munich, GermanyExercise Biology Group, Department of Sport and Health Sciences, Technical University of Munich, Munich, GermanyGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, GermanyGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, GermanyChair of Experimental Genetics, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, GermanyGerman Center for Diabetes Research, Neuherberg, GermanyExercise Biology Group, Department of Sport and Health Sciences, Technical University of Munich, Munich, GermanyEndurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest that several endurance-associated traits are ≈50% inherited. However, we still poorly understand what DNA sequence variants contribute to endurance heritability. To address this issue, we conducted a systematic review to identify genes whose experimental loss or gain-of-function increases endurance capacity in mice. We found 31 genes including two isoforms of Ppargc1a whose manipulation increases running or swimming endurance performance by up to 1800%. Genes whose gain-of-function increases endurance are Adcy5, Adcy8, Hk2, Il15, Mef2c, Nr4a3, Pck1 (Pepck), Ppard, Ppargc1a (both the a and b isoforms of the protein Pgc-1α), Ppargc1b, Ppp3ca (calcineurin), Scd1, Slc5a7, Tfe3, Tfeb, Trib3 & Trpv1. Genes whose loss-of-function increases endurance in mice are Actn3, Adrb2, Bdkrb2, Cd47, Crym, Hif1a, Myoz1, Pappa, Pknox1, Pten, Sirt4, Thbs1, Thra, and Tnfsf12. Of these genes, human DNA sequence variants of ACTN3, ADCY5, ADRB2, BDKRB2, HIF1A, PPARD, PPARGC1A, PPARGC1B, and PPP3CA are also associated with endurance capacity and/or VO2max trainability suggesting evolutionary conservation between mice and humans. Bioinformatical analyses show that there are numerous amino acid or copy number-changing DNA variants of endurance genes in humans, suggesting that genetic variation of endurance genes contributes to the variation of human endurance capacity, too. Moreover, several of these genes/proteins change their expression or phosphorylation in skeletal muscle or the heart after endurance exercise, suggesting a role in the adaptation to endurance exercise.https://www.frontiersin.org/article/10.3389/fphys.2019.00262/fullendurancerunningtransgenic micegeneticsmitochondrial biogenesisGWAS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fakhreddin Yaghoob Nezhad Sander A. J. Verbrugge Martin Schönfelder Lore Becker Martin Hrabě de Angelis Martin Hrabě de Angelis Martin Hrabě de Angelis Henning Wackerhage |
spellingShingle |
Fakhreddin Yaghoob Nezhad Sander A. J. Verbrugge Martin Schönfelder Lore Becker Martin Hrabě de Angelis Martin Hrabě de Angelis Martin Hrabě de Angelis Henning Wackerhage Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review Frontiers in Physiology endurance running transgenic mice genetics mitochondrial biogenesis GWAS |
author_facet |
Fakhreddin Yaghoob Nezhad Sander A. J. Verbrugge Martin Schönfelder Lore Becker Martin Hrabě de Angelis Martin Hrabě de Angelis Martin Hrabě de Angelis Henning Wackerhage |
author_sort |
Fakhreddin Yaghoob Nezhad |
title |
Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review |
title_short |
Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review |
title_full |
Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review |
title_fullStr |
Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review |
title_full_unstemmed |
Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review |
title_sort |
genes whose gain or loss-of-function increases endurance performance in mice: a systematic literature review |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2019-03-01 |
description |
Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest that several endurance-associated traits are ≈50% inherited. However, we still poorly understand what DNA sequence variants contribute to endurance heritability. To address this issue, we conducted a systematic review to identify genes whose experimental loss or gain-of-function increases endurance capacity in mice. We found 31 genes including two isoforms of Ppargc1a whose manipulation increases running or swimming endurance performance by up to 1800%. Genes whose gain-of-function increases endurance are Adcy5, Adcy8, Hk2, Il15, Mef2c, Nr4a3, Pck1 (Pepck), Ppard, Ppargc1a (both the a and b isoforms of the protein Pgc-1α), Ppargc1b, Ppp3ca (calcineurin), Scd1, Slc5a7, Tfe3, Tfeb, Trib3 & Trpv1. Genes whose loss-of-function increases endurance in mice are Actn3, Adrb2, Bdkrb2, Cd47, Crym, Hif1a, Myoz1, Pappa, Pknox1, Pten, Sirt4, Thbs1, Thra, and Tnfsf12. Of these genes, human DNA sequence variants of ACTN3, ADCY5, ADRB2, BDKRB2, HIF1A, PPARD, PPARGC1A, PPARGC1B, and PPP3CA are also associated with endurance capacity and/or VO2max trainability suggesting evolutionary conservation between mice and humans. Bioinformatical analyses show that there are numerous amino acid or copy number-changing DNA variants of endurance genes in humans, suggesting that genetic variation of endurance genes contributes to the variation of human endurance capacity, too. Moreover, several of these genes/proteins change their expression or phosphorylation in skeletal muscle or the heart after endurance exercise, suggesting a role in the adaptation to endurance exercise. |
topic |
endurance running transgenic mice genetics mitochondrial biogenesis GWAS |
url |
https://www.frontiersin.org/article/10.3389/fphys.2019.00262/full |
work_keys_str_mv |
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