Single Genetic Determinant that Prevents Sex Reversal in C57BL-YPOS Congenic Mice

• Published in: Biochemical genetics Vol. 38; no. 5-6; pp. 119 - 137
• Main Authors: Whitney, J B, Mills, T M, Lewis, R W, Wartell, R, Abney, T O
• Format: Journal Article
• Language: English
• Published: United States Kluwer Academic Publishers-Plenum Publishers 01-06-2000; Springer Nature B.V
• Subjects: Alpha-Globulins - urine; Animals; Breeding; Chromosomes; Disorders of Sex Development; DNA; DNA-Binding Proteins - genetics; Embryos; Female; Genetics; Hermaphrodites; Male; Males; Mice; Mice, Congenic; Mice, Inbred C57BL; Mus musculus; Nuclear Proteins; Organ Size; Ovary - growth & development; Phenotype; Polymorphism, Restriction Fragment Length; Proteins; Selective breeding; Sex; Sex determination; Sex Determination Processes; Sex reversal; Sex-Determining Region Y Protein; SRY protein; Testes; Testis - growth & development; Testosterone; Testosterone - blood; Transcription Factors; X Chromosome - genetics; Y chromosome; Y Chromosome - genetics
• ISSN: 0006-2928; 1573-4927
• DOI: 10.1023/A:1001935012134

Sex determination in the mammalian embryo begins with the activation of a gene on the Y chromosome which triggers a cascade of events that lead to male development. The mechanism by which this gene, designated SRY in humans and Sry in mice (sex determining region of the Y chromosome), is activated remains unknown. Likewise, the downstream target genes for Sry remain unidentified at present. C57BL mice carrying a Y chromosome from Mus musculus musculus or molossinus develop normally as males. In contrast, C57BL/6 mice with the Y chromosome from M. m. domesticus often show sex reversal, i.e., develop as XY females. It has been documented that C57BL mice with the Y chromosome from Poschiavinus (YᴾᴼS), a domesticus subtype, always develop as females or hermaphrodites. This suggests that a C57BL gene either up- or downstream of Sry is ineffective in interacting with Sry, which then compromises the processes that lead to normal male sex development. Nonetheless, by selective breeding, we have been able to generate a sex reversal-resistant C57BL/6-congenic strain of mice in which the XYᴾᴼS individuals consistently develop as normal males with bilateral testes. Because the resistance to sex reversal was transferred from strain 129S1/Sv (nonalbino) by simple selection over 13 backcross generations, it is inferred that a single autosomal gene or chromosomal region confers resistance to the sex reversal that would otherwise result. XYᴾᴼS normal males generated in these crosses were compared to XYᴾᴼS abnormal individuals and to C57BL/6 controls for sexual phenotype, gonadal weight, serum testosterone, and major urinary protein (MUP) level. A clear correlation was found among phenotypic sex, MUP level, and testis weight in the males and in the incompletely masculinized XYᴾᴼS mice. The fully masculinized males of the congenic strain resemble C57BL/6 males in the tested parameters. DNA analysis confirmed that these males, in fact, carry the YᴾᴼS Sry gene.