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Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken

Runting and stunting syndrome (RSS), which is characterized by low body weight, generally occurs early in life and leads to considerable economic losses in the commercial broiler industry. Our previous study has suggested that RSS is associated with mitochondria dysfunction in sex-linked dwarf (SLD)...

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Autores principales: Hu, Bowen, Yang, Minmin, Liao, Zhiying, Wei, Haohui, Zhao, Changbin, Li, Dajian, Hu, Shuang, Jiang, Xinsheng, Shi, Meiqing, Luo, Qingbin, Zhang, Dexiang, Nie, Qinghua, Zhang, Xiquan, Li, Hongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381202/
https://www.ncbi.nlm.nih.gov/pubmed/32766243
http://dx.doi.org/10.3389/fcell.2020.00581
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author Hu, Bowen
Yang, Minmin
Liao, Zhiying
Wei, Haohui
Zhao, Changbin
Li, Dajian
Hu, Shuang
Jiang, Xinsheng
Shi, Meiqing
Luo, Qingbin
Zhang, Dexiang
Nie, Qinghua
Zhang, Xiquan
Li, Hongmei
author_facet Hu, Bowen
Yang, Minmin
Liao, Zhiying
Wei, Haohui
Zhao, Changbin
Li, Dajian
Hu, Shuang
Jiang, Xinsheng
Shi, Meiqing
Luo, Qingbin
Zhang, Dexiang
Nie, Qinghua
Zhang, Xiquan
Li, Hongmei
author_sort Hu, Bowen
collection PubMed
description Runting and stunting syndrome (RSS), which is characterized by low body weight, generally occurs early in life and leads to considerable economic losses in the commercial broiler industry. Our previous study has suggested that RSS is associated with mitochondria dysfunction in sex-linked dwarf (SLD) chickens. However, the molecular mechanism of RSS remains unknown. Based on the molecular diagnostics of mitochondrial diseases, we identified a recessive mutation c. 409G > A (p. Ala137Thr) of Twinkle mitochondrial DNA helicase (TWNK) gene and mitochondrial DNA (mtDNA) depletion in RSS chickens’ livers from strain N301. Bioinformatics investigations supported the pathogenicity of the TWNK mutation that is located on the extended peptide linker of Twinkle primase domain and might further lead to mtDNA depletion in chicken. Furthermore, overexpression of wild-type TWNK increases mtDNA copy number, whereas overexpression of TWNK A137T causes mtDNA depletion in vitro. Additionally, the TWNK c. 409G > A mutation showed significant associations with body weight, daily gain, pectoralis weight, crureus weight, and abdominal fat weight. Taken together, we corroborated that the recessive TWNK c. 409G > A (p. Ala137Thr) mutation is associated with RSS characterized by mtDNA depletion in SLD chicken.
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spelling pubmed-73812022020-08-05 Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken Hu, Bowen Yang, Minmin Liao, Zhiying Wei, Haohui Zhao, Changbin Li, Dajian Hu, Shuang Jiang, Xinsheng Shi, Meiqing Luo, Qingbin Zhang, Dexiang Nie, Qinghua Zhang, Xiquan Li, Hongmei Front Cell Dev Biol Cell and Developmental Biology Runting and stunting syndrome (RSS), which is characterized by low body weight, generally occurs early in life and leads to considerable economic losses in the commercial broiler industry. Our previous study has suggested that RSS is associated with mitochondria dysfunction in sex-linked dwarf (SLD) chickens. However, the molecular mechanism of RSS remains unknown. Based on the molecular diagnostics of mitochondrial diseases, we identified a recessive mutation c. 409G > A (p. Ala137Thr) of Twinkle mitochondrial DNA helicase (TWNK) gene and mitochondrial DNA (mtDNA) depletion in RSS chickens’ livers from strain N301. Bioinformatics investigations supported the pathogenicity of the TWNK mutation that is located on the extended peptide linker of Twinkle primase domain and might further lead to mtDNA depletion in chicken. Furthermore, overexpression of wild-type TWNK increases mtDNA copy number, whereas overexpression of TWNK A137T causes mtDNA depletion in vitro. Additionally, the TWNK c. 409G > A mutation showed significant associations with body weight, daily gain, pectoralis weight, crureus weight, and abdominal fat weight. Taken together, we corroborated that the recessive TWNK c. 409G > A (p. Ala137Thr) mutation is associated with RSS characterized by mtDNA depletion in SLD chicken. Frontiers Media S.A. 2020-07-14 /pmc/articles/PMC7381202/ /pubmed/32766243 http://dx.doi.org/10.3389/fcell.2020.00581 Text en Copyright © 2020 Hu, Yang, Liao, Wei, Zhao, Li, Hu, Jiang, Shi, Luo, Zhang, Nie, Zhang and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Hu, Bowen
Yang, Minmin
Liao, Zhiying
Wei, Haohui
Zhao, Changbin
Li, Dajian
Hu, Shuang
Jiang, Xinsheng
Shi, Meiqing
Luo, Qingbin
Zhang, Dexiang
Nie, Qinghua
Zhang, Xiquan
Li, Hongmei
Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
title Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
title_full Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
title_fullStr Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
title_full_unstemmed Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
title_short Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
title_sort mutation of twnk gene is one of the reasons of runting and stunting syndrome characterized by mtdna depletion in sex-linked dwarf chicken
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381202/
https://www.ncbi.nlm.nih.gov/pubmed/32766243
http://dx.doi.org/10.3389/fcell.2020.00581
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