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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

Published on Dec 1, 2017in Scientific Reports4.011
· DOI :10.1038/s41598-017-04117-6
Tatsuo Kido12
Estimated H-index: 12
(UCSF: University of California, San Francisco),
Zhaoyu Sun1
Estimated H-index: 1
(UCSF: University of California, San Francisco),
Yun-Fai Chris Lau29
Estimated H-index: 29
(UCSF: University of California, San Francisco)
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.
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Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Grant/Award Number: DS ProgramDS-1750212PROEX-1 669479PROEX-33002010073P7; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Grant/Award Number: 2011/04956-62011/ 14658-22014/00041-12014/00591-12014/ 10488-32015/06281-7; Universidade Federal do ABC, Grant/Award Number: Institutional Scholarship; UFABC; CAPES, Grant/Award Number: DS-1750212; FAPESP, Grant/Award Numbers: 2014/10488-3, 2011/04956-6, 2014/00591-1, 2014/00041-1, 2015/06...
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