C57BL/6J-T-associated sex reversal in mice is caused by reduced expression of a Mus domesticus Sry allele.
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 T(hp) and T(Orl), (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 T(Orl)/+ XY(AKR) 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 T(Orl)/+ 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 T(Orl)/+ XY(AKR) 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 T(Orl)/+ XY(AKR) mice results from a biologically insufficient level of Sry expression, allowing the ovarian development pathway to proceed.
Washburn
L L
LL
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Albrecht
K H
KH
Eicher
E M
EM
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D012734:Disorders of Sex Development; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016366:Open Reading Frames; D010053:Ovary / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D051876:Sex-Determining Region Y Protein; D013997:Time Factors; D014157:Transcription Factors; D019076:Transgenes; D014998:Y Chromosome
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D014157:Transcription Factors