The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice

English version

Autoři: Stefan Bagheri-Fam ^aff001; Huijun Chen ^aff002; Sean Wilson ^aff003; Katie Ayers ^aff003; James Hughes ^aff005; Frederique Sloan-Bena ^aff006; Pierre Calvel ^aff007; Gorjana Robevska ^aff003; Beatriz Puisac ^aff008; Kamila Kusz-Zamelczyk ^aff009; Stefania Gimelli ^aff006; Anna Spik ^aff009; Jadwiga Jaruzelska ^aff009; Alina Warenik-Szymankiewicz ^aff010; Sultana Faradz ^aff011; Serge Nef ^aff006; Juan Pié ^aff008; Paul Thomas ^aff005; Andrew Sinclair ^aff003; Dagmar Wilhelm ^aff001
Působiště autorů: Department of Anatomy & Neuroscience, The University of Melbourne, Melbourne, Australia ^aff001; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia ^aff002; Murdoch Children’s Research Institute, Melbourne, Australia ^aff003; Department of Paediatrics, The University of Melbourne, Melbourne, Australia ^aff004; School of Biological Sciences, University of Adelaide, Adelaide, Australia ^aff005; Service of Genetic Medicine, University Geneva Hospitals, Geneva, Switzerland ^aff006; Department of Genetics, Medicine & Development, University of Geneva, Geneva, Switzerland ^aff007; Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragon, Zaragoza, Spain ^aff008; Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland ^aff009; Department of Gynecological Endocrinology Poznan University of Medical Sciences, Poznan, Poland ^aff010; Center for Biomedical Research Faculty of Medicine Diponegoro University (FMDU), Semarang, Indonesia ^aff011
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227411

Souhrn

Disorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at the molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding a metabolic enzyme in the liver important for energy production from fatty acids, that shows an unusual expression pattern in developing fetal mouse gonads. Shortly after gonadal sex determination it is up-regulated in the developing testes following a very similar spatial and temporal pattern as the male-determining gene Sry in Sertoli cells before switching to ovarian enriched expression. To test if Hmgcs2 is important for gonad development in mammals, we pursued two lines of investigations. Firstly, we generated Hmgcs2-null mice using CRISPR/Cas9 and found that these mice had gonads that developed normally even on a sensitized background. Secondly, we screened 46,XY DSD patients with gonadal dysgenesis and identified two unrelated patients with a deletion and a deleterious missense variant in HMGCS2 respectively. However, both variants were heterozygous, suggesting that HMGCS2 might not be the causative gene. Analysis of a larger number of patients in the future might shed more light into the possible association of HMGCS2 with human gonadal development.

Klíčová slova:

Cell differentiation – Embryos – Gene expression – Germ cells – Gonads – Ovaries – Testes – Sertoli cells

Zdroje

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The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice

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