Anogenital distance (AGD), a sex differentiation marker in mice (Mus m
usculus), is thought to be a secondary sexual trait exclusively regula
ted by androgens during development. However, recent studies suggest t
hat some so-called secondary sexual traits may be influenced by sex-ch
romosomal genotype. To explore this question further we studied the AG
D of the XXSxr 'sex-reversed' mouse, which has adequate androgens for
masculinization. The AGDs of adult and prepubertal XY, XYSxr carrier,
XXSxr 'sex-reversed' and XX mice were measured. We found that adult XX
Sxr 'sex-reversed' mice (which we refer to as pseudomales) and XYSxr c
arriers have shorter mean AGDs than their XY siblings. Prepubertal XXS
xr animals also have shorter mean AGDs than their XY siblings when AGD
is expressed as a proportion of body length. XX adult and prepubertal
mice have significantly shorter AGDs than the other genotypes at simi
lar stages of development. The differences in AGD between adult and pr
epubertal XY and XXSxr sibs, and adult XY and XYSxr sibs, reported her
e, do not appear to be due to androgen levels, since adult testicular
and serum testosterone levels are higher in pseudomales and carriers t
han in XY mice, and fetal pseudomale androgen levels also appear to be
at least as high as those of normal males. Furthermore, the AGD diffe
rences between genotypes are not correlated to differences in testis s
ize. We conclude that the differences are likely to be due to a tissue
specific effect of the genetic constitution of the individuals, as is
the case with scrotal development in the marsupial Macropus eugenii (
the tammar wallaby).