Sex determination in the mammalian embryo begins with the activation of a g
ene on the Y chromosome which triggers a cascade of events that lead to mal
e development. The mechanism by which this gene, designated SRY in humans a
nd Sry in mice (sex determining region of the Y chromosome), is activated r
emains unknown. Likewise, the downstream target genes for Sry remain uniden
tified at present. C57BL mice carrying a Y chromosome from Mus musculus mus
culus or molossinus develop normally as males. In contrast, C57BL/6 mice wi
th the Y chromosome from M. m. domesticus often show sex reversal, i.e., de
velop as XY females. It has been documented that C57BL mice with the Y chro
mosome from Poschiavinus (Y-POS), a domesticus subtype, always develop as f
emales or hermaphrodites. This suggests that a C57BL gene either up- or dow
nstream of Sry is ineffective in interacting with Sry, which then compromis
es the processes that lend 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 s
ex reversal was transferred from strain 129S1/Sv (nonalbino) by simple sele
ction over 13 backcross generations, it is inferred that a single autosomal
gene or chromosomal region confers resistance to the sex reversal that wou
ld otherwise result. XYPOS normal males generated in these crosses were com
pared to XYPOS abnormal individuals and to C57BL/6 controls for sexual phen
otype, gonadal weight, serum testosterone, and major urinary protein (MUP)
level. A clear correlation was found among phenotypic sex, MUP level, and t
estis 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 Y-POS Sry gene.