Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice

Abstract Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is a...

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Autores principales:	Tatsuo Kido, Zhaoyu Sun, Yun-Fai Chris Lau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41ff5c0cb38e41218f0c9cb9f402d29c
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spelling	oai:doaj.org-article:41ff5c0cb38e41218f0c9cb9f402d29c2021-12-02T16:07:58ZAberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice10.1038/s41598-017-04117-62045-2322https://doaj.org/article/41ff5c0cb38e41218f0c9cb9f402d29c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04117-6https://doaj.org/toc/2045-2322Abstract Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRYON) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRYON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.Tatsuo KidoZhaoyu SunYun-Fai Chris LauNature 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 Tatsuo Kido Zhaoyu Sun Yun-Fai Chris Lau Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
description	Abstract Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRYON) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRYON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.
format	article
author	Tatsuo Kido Zhaoyu Sun Yun-Fai Chris Lau
author_facet	Tatsuo Kido Zhaoyu Sun Yun-Fai Chris Lau
author_sort	Tatsuo Kido
title	Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
title_short	Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
title_full	Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
title_fullStr	Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
title_full_unstemmed	Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
title_sort	aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/41ff5c0cb38e41218f0c9cb9f402d29c
work_keys_str_mv	AT tatsuokido aberrantactivationofthehumansexdetermininggeneinearlyembryonicdevelopmentresultsinpostnatalgrowthretardationandlethalityinmice AT zhaoyusun aberrantactivationofthehumansexdetermininggeneinearlyembryonicdevelopmentresultsinpostnatalgrowthretardationandlethalityinmice AT yunfaichrislau aberrantactivationofthehumansexdetermininggeneinearlyembryonicdevelopmentresultsinpostnatalgrowthretardationandlethalityinmice
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Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice

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