Inheritance of T-associated sex reversal in mice.

We previously identified a primary sex-determining locus, Tas, on mouse Chr 17 that causes ovarian tissue development in C57BL/6J Thp/+ and TOrl/+ individuals if the AKR/JY chromosome is present. We hypothesized that Tas is located within the region of Chr 17 deleted by Thp and TOrl and that C57BL/6J carries a diagnostic Tas allele, based on the observation that ovarian tissue develops in XY mice when Thp is on a C57BL/6J inbred strain background, whereas normal testicular development occurs when Thp is on a C3H/HeSnJ inbred strain background. To test this hypothesis, we mated (C57BL/6J x C3H/HeSnJ)F1 females to C57BL/6J Thp/+ hermaphrodites. As expected, half of the XY Thp/+ offspring developed ovarian and testicular tissue while half developed exclusively testicular tissue. Unexpectedly, the inheritance of selected Chr 17 molecular loci was independent of gonadal development, as half of the male and hermaphroditic offspring inherited C3H/HeSnJ-derived Chr 17 loci and half inherited C57BL/6J-derived Chr 17 loci. We conclude that for ovarian tissue to develop in an XY Thp/+ or XY TOrl/+ individual (1) Tas must be present in a hemizygous state, which is accomplished by heterozygosity for the Thp or TOrl deletions; (2) the AKR/J-derived Y chromosome must be present; and (3) an additional locus involved in primary sex determination must be present in a homozygous C57BL/6J state. This newly identified gene may be one of the previously defined loci, tda-1 or tda-2.