title: Gonadal effects of a mouse Denys-Drash syndrome mutation.
abstract: Gonadal effects of the Denys-Drash syndrome (DDS) mutation Wt1(tmT396 )were examined in chimaeric and heterozygous mice. Since the only heterozygote was 41,XXY, Sertoli cell function was assessed by comparison with age-matched control XXY testes. Control XXY Sertoli cells showed immuno-expression of WT1 and androgen receptor (AR) indistinguishable from wild-type (40,XY), but expressed anti-Mullerian hormone (AMH). In contrast, DDS Sertoli cells showed only faint immuno-expression of WT1 and did not express AR or AMH. While XY<-->XY DDS chimaeras were male, XX<-->XY chimaeras were predominantly female. In the rare XX<-->XY DDS males the Sertoli cell lineage was largely derived from Wt1 mutant XY cells. We conclude that DDS mutant cells can form Sertoli cells, that the dominant mutation does not cause male sex reversal in mice but distorts the sex ratio of XX<-->XY chimaeras, and that there may be a link between WT1, AMH and AR expression by Sertoli cells in vivo.
authors.affiliation: Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, Western General Hospital, Crewe Road, EH4 2XU Edinburgh, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Patek
authors.forename: P T K
authors.initials: PT
authors.lastname: Saunders
authors.forename: C G
authors.initials: CG
authors.lastname: Miles
authors.forename: R L
authors.initials: RL
authors.lastname: Berry
authors.forename: N D
authors.initials: ND
authors.lastname: Hastie
authors.forename: R M
authors.initials: RM
authors.lastname: Sharpe
authors.forename: M L
authors.initials: ML
authors.lastname: Hooper
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone; D002678:Chimera / Q000235:genetics; D030321:Denys-Drash Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology; D012744:Sex Ratio; D013735:Testicular Hormones / Q000235:genetics; D013737:Testis / Q000378:metabolism / Q000473:pathology*; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D006023:Glycoproteins; D011944:Receptors, Androgen; D013735:Testicular Hormones; D025721:WT1 Proteins; D054304:Anti-Mullerian Hormone