title: A major locus on mouse chromosome 18 controls XX sex reversal in Odd Sex (Ods) mice.
abstract: We have previously reported a dominant mouse mutant, Odd sex (Ods), in which XX Ods/+ mice on the FVB/N background show complete sex reversal, associated with expression of Sox9 in the fetal gonads. Remarkably, when crossed to the A/J strain approximately 95% of the (AXFVB) F(1) XX Ods/+ mice developed as fully fertile, phenotypic females, the remainder developing as males or hermaphrodites. Using a (AXFVB) F(2) population, we conducted a genome-wide linkage scan to identify the number and chromosomal location of potential Ods modifier genes. A single major locus termed Odsm1 was mapped to chromosome 18, tightly linked to D18Mit189 and D18Mit210. Segregation at this locus could account for the presence of sex reversal in 100% of XX Ods/+ mice which develop as males, for the absence of sex reversal in approximately 92% of XX Ods/+ mice which develop as females, and for the mixed sexual phenotype in approximately 72% of XX Ods/+ mice that develop with ambiguous genitalia. We propose that homozygosity for the FVB-derived allele strongly favors Ods sex reversal, whereas homozygosity for the A/J-derived allele inhibits it. In mice heterozygous at Odsm1, the phenotypic outcome, male, female or hermaphrodite, is determined by a complex interaction of several minor modifying loci. The close proximity of Smad2, Smad7 and Smad4 to D18Mit189/210 provides a potential mechanism through which Odsm1 might act.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Qin
authors.forename: Christophe
authors.initials: C
authors.lastname: Poirier
authors.forename: Cavatina
authors.initials: C
authors.lastname: Truong
authors.forename: Armin
authors.initials: A
authors.lastname: Schumacher
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Agoulnik
authors.forename: Colin E
authors.initials: CE
authors.lastname: Bishop
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D012734:Disorders of Sex Development / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008297:Male; D051379:Mice; D010375:Pedigree; D019849:Sex Determination Processes; D014960:X Chromosome