C57BL/6J-T-associated sex reversal in mice is caused by reduced expressionof a Mus domesticus Sry allele

C57BL/6j-T-associated sex reversal (B6-TAS) in XY mice results in ovarian d evelopment and involves (1) hemizygosity for Tas, a gene located in the reg ion of Chromosome 17 deleted in T-hp and T-Orl, (2) homozygosity for one or more B6-derived autosomal genes, and (3) the presence of the AKRY chromoso me. Here we report results from experiments designed to investigate the Y c hromosome component of this sex reversal. Testis development was restored i n B6 T-Orl /+ XYAKR mice carrying a Mus musculus Sry transgene. In addition , two functionally different classes of M. domesticus Sty alleles were iden tified among eight standard and two wild-derived inbred strains. One class, which includes. AKR, did not initiate normal testis development in B6 T-Or d/+ XY mice, whereas the other did. DNA sequence analysis of the Sry ORF an d a 5 ' 800-bp segment divided these inbred strains into the same groups. F inally, we found that Sry is transcribed in B6 T-Ord/+ XYAKR fetal gonads b ut at a reduced level. These results pinpoint, Sry as the Y-linked componen t of BG-TAS. We hypothesize that the inability of specific AL domesticus Sr y alleles to initiate normal testis development in BG T-Ord/+ XYAKR mice re sults from a biologically insufficient level of Sry expression, allowing th e ovarian development pathway to proceed.