Genetics, Vol. 158, 1675-1681, August 2001, Copyright © 2001

C57BL/6J-T-Associated Sex Reversal in Mice Is Caused by Reduced Expression of a Mus domesticus Sry Allele

Linda L. Washburna, Kenneth H. Albrechta, and Eva M. Eichera
a The Jackson Laboratory, Bar Harbor, Maine 04609

Corresponding author: Eva M. Eicher, The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609., eme{at}jax.org (E-mail)

Communicating editor: N. A. JENKINS

C57BL/6J-T-associated sex reversal (B6-TAS) in XY mice results in ovarian development and involves (1) hemizygosity for Tas, a gene located in the region of Chromosome 17 deleted in Thp and TOrl, (2) homozygosity for one or more B6-derived autosomal genes, and (3) the presence of the AKR Y chromosome. Here we report results from experiments designed to investigate the Y chromosome component of this sex reversal. Testis development was restored in B6 TOrl/+ XYAKR mice carrying a Mus musculus Sry transgene. In addition, two functionally different classes of M. domesticus Sry alleles were identified among eight standard and two wild-derived inbred strains. One class, which includes AKR, did not initiate normal testis development in B6 TOrl/+ XY mice, whereas the other did. DNA sequence analysis of the Sry ORF and a 5' 800-bp segment divided these inbred strains into the same groups. Finally, we found that Sry is transcribed in B6 TOrl/+ XYAKR fetal gonads but at a reduced level. These results pinpoint Sry as the Y-linked component of B6-TAS. We hypothesize that the inability of specific M. domesticus Sry alleles to initiate normal testis development in B6 TOrl/+ XYAKR mice results from a biologically insufficient level of Sry expression, allowing the ovarian development pathway to proceed.




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