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

Genetics. 2001 Aug;158(4):1675-81. doi: 10.1093/genetics/158.4.1675.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • Disorders of Sex Development*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Open Reading Frames
  • Ovary / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sex-Determining Region Y Protein
  • Time Factors
  • Transcription Factors*
  • Transgenes
  • Y Chromosome

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Sex-Determining Region Y Protein
  • Sry protein, mouse
  • Transcription Factors