Genetic differences between C57BL/6 substrains affect the process of testis differentiation in Y^POS mice

Abstract

C57BL/6J-XY POS (B6J-XY POS ) mice, which have the Y chromosome derived from Mus musculus poschiavinus on a B6J genetic background, form ovotestes or ovaries. Previously, we replaced the genetic background of B6J-XY POS mice with B6N and found that individuals with testes also appeared in addition to those with ovaries or ovotestes. To investigate the effect of the B6J genetic sequence on the testis differentiation, the genetic background of B6N-XY POS mice was replaced with B6J again. The recovery of the B6J genetic background significantly decreased the incidence of testes; only ovaries developed. These results indicate that the testicular differentiation process tends to be perturbed especially in the B6J substrain. This shows the importance of substrain differences in mice usually treated as B6 collectively.

Substrain differences in Sry expression at the stage of sex determination in C57BL/6 mouse strains

“…For example, different gonadal phenotypes have appeared from the same genetic background when Mus. musculus Domesticus -type Sry, which has low stability, was replaced, such as B6-XY POS and B6-XY TIR [ 2 , 3 , 8 , 24 , 41 , 47 ]. In contrast, other strains, such as DBA/2J (D2) and 129S1/SvJ (129S), are resistant to the disturbance of sexual differentiation by M. m. Domesticus -type Sry [ 12 , 26 ].…”

“…In fact, it has been reported that the timing of Sry expression and the gonadal phenotype are different in B6-XY POS mice, a model of disorders of sex development (DSD) with a B6 strain background, due to the different genetic background among B6 substrain [ 10 , 11 , 42 , 47 ]. XY POS mice with the background of the Jackson Lab strain, which is the B6J substrain, have been reported to form ovaries or ovotestes [ 10 , 11 ].…”

“…On the other hand, B6-XY POS mice with the B6NCrSlc genetic background had delayed Sry expression by 2~3 ts, and some individuals formed testes in addition to ovaries and ovotestes [ 42 ]. In B6-XY POS mice in which the genetic background was replaced by B6JJmsSlc, ovaries formed in all individuals [ 47 ]. Based on these differences in gonadal phenotype among substrains, we hypothesized that there are differences in Sry expression among substrains even in wild-type B6 mice.…”

Establishment of an organ culture system to induce Sertoli cell differentiation from undifferentiated mouse gonads

“…There are differences in the Sry sequence among mouse strains, and the capacity of testicular formation is different [1,4,30]. Sry sequences with weak activity harbored in many mouse strains with disorders of sex development may delay Sry expression and cause sex reversal, but the reason for such delayed Sry expression is unknown [2,12,36,39,40,44]. Perturbation of histone demethylase Kdm3a (lysine (K)-specific demethylase 3A; Jmjd1a) expression also causes suppression of Sry, and causes sex reversal in the male gonads [19,20,21].…”