title: Male-to-female sex reversal in M33 mutant mice.
abstract: Polycomb genes in Drosophila maintain the repressed state of homeotic and other developmentally regulated genes by mediating changes in higher-order chromatin structure. M33, a mouse homologue of Polycomb, was isolated by means of the structural similarity of its chromodomain. The fifth exon of M33 contains a region of homology shared by Drosophila and Xenopus. In Drosophila, its deletion results in the loss of Polycomb function. Here we have disrupted M33 in mice by inserting a poly(A) capture-type neo(r) targeting vector into its fifth exon. More than half of the resultant M33cterm/M33cterm mutant mice died before weaning, and survivors showed male-to-female sex reversal. Formation of genital ridges was retarded in both XX and XY M33cterm/M33cterm embryos. Gonadal growth defects appeared near the time of expression of the Y-chromosome-specific Sry gene, suggesting that M33 deficiency may cause sex reversal by interfering with steps upstream of Sry. M33cterm/M33cterm mice may be a valuable model in which to test opposing views regarding sex determination.
authors.affiliation: Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo, Japan. kan@libra.ls.mkagaku.co.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Katoh-Fukui
authors.forename: R
authors.initials: R
authors.lastname: Tsuchiya
authors.forename: T
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakahara
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.forename: T
authors.initials: T
authors.lastname: Higashinakagawa
mesh_terms: D000818:Animals; D002678:Chimera; D012734:Disorders of Sex Development; D005260:Female; D005808:Genes, Recessive; D005835:Genitalia / Q000002:abnormalities / Q000196:embryology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010053:Ovary / Q000196:embryology; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics*; D019849:Sex Determination Processes; D013234:Stem Cells; D013737:Testis / Q000196:embryology
chemical_list: C570426:Cbx2 protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1