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

Librarian's Comment : The gonadal expression of the SRY gene initiates male sex determination. Yet, SRY is expressed in other tissues, both during development and in adult life. The exact function, if any, of non-gonadal SRY expression remains to be determined, yet it has been argued that it may be directly involved in the masculinization of somatic tissues. In this paper, the authors have developed a transgenic mouse system that allows human SRY to be expressed in a tissue-specific manner. This system opens the door to the precise aberrant activation of SRY in selected cell types, a prerequisite to understanding what is the possible function of SRY outside of the gonads.
Published in : Scientific reports
Authors : Kido T, Sun Z, Lau YC


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 (hSRY(ON)) 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 hSRY(ON) 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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