Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis

Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn −/− mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are i...

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Autores principales:	Hung-Chih Chen, Yu-Feng Chin, David J. Lundy, Chung-Tiang Liang, Ya-Hui Chi, Paolin Kuo, Patrick C. H. Hsieh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/574d967a664547919ea2d5da8ee9fe37
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spelling	oai:doaj.org-article:574d967a664547919ea2d5da8ee9fe372021-12-02T12:30:43ZUtrophin Compensates dystrophin Loss during Mouse Spermatogenesis10.1038/s41598-017-05993-82045-2322https://doaj.org/article/574d967a664547919ea2d5da8ee9fe372017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05993-8https://doaj.org/toc/2045-2322Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn −/− mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn +/− mouse models, we demonstrate the contribution of Dp427 (full-length dystrophin) and utrophin to testis and epididymis development, as well as spermatogenesis. We show that Dp427 deficiency disturbed the balance between proliferation and apoptosis of germ cells during spermatogenesis, which was further disrupted with utrophin haplodeficiency, deciphering a compensatory role of utrophin for dystrophin in the male reproductive system. In the spermatozoa, we have found a compensatory response of utrophin to dystrophin deficiency - namely the upregulation and relocation of utrophin to the flagellar midpiece. This study demonstrates the contribution of Dp427 and utrophin in male fertility, suggesting a potential pathology in DMD patients.Hung-Chih ChenYu-Feng ChinDavid J. LundyChung-Tiang LiangYa-Hui ChiPaolin KuoPatrick C. H. HsiehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hung-Chih Chen Yu-Feng Chin David J. Lundy Chung-Tiang Liang Ya-Hui Chi Paolin Kuo Patrick C. H. Hsieh Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
description	Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn −/− mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn +/− mouse models, we demonstrate the contribution of Dp427 (full-length dystrophin) and utrophin to testis and epididymis development, as well as spermatogenesis. We show that Dp427 deficiency disturbed the balance between proliferation and apoptosis of germ cells during spermatogenesis, which was further disrupted with utrophin haplodeficiency, deciphering a compensatory role of utrophin for dystrophin in the male reproductive system. In the spermatozoa, we have found a compensatory response of utrophin to dystrophin deficiency - namely the upregulation and relocation of utrophin to the flagellar midpiece. This study demonstrates the contribution of Dp427 and utrophin in male fertility, suggesting a potential pathology in DMD patients.
format	article
author	Hung-Chih Chen Yu-Feng Chin David J. Lundy Chung-Tiang Liang Ya-Hui Chi Paolin Kuo Patrick C. H. Hsieh
author_facet	Hung-Chih Chen Yu-Feng Chin David J. Lundy Chung-Tiang Liang Ya-Hui Chi Paolin Kuo Patrick C. H. Hsieh
author_sort	Hung-Chih Chen
title	Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
title_short	Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
title_full	Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
title_fullStr	Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
title_full_unstemmed	Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
title_sort	utrophin compensates dystrophin loss during mouse spermatogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/574d967a664547919ea2d5da8ee9fe37
work_keys_str_mv	AT hungchihchen utrophincompensatesdystrophinlossduringmousespermatogenesis AT yufengchin utrophincompensatesdystrophinlossduringmousespermatogenesis AT davidjlundy utrophincompensatesdystrophinlossduringmousespermatogenesis AT chungtiangliang utrophincompensatesdystrophinlossduringmousespermatogenesis AT yahuichi utrophincompensatesdystrophinlossduringmousespermatogenesis AT paolinkuo utrophincompensatesdystrophinlossduringmousespermatogenesis AT patrickchhsieh utrophincompensatesdystrophinlossduringmousespermatogenesis
_version_	1718394336550322176

Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis

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