Sex-specific modifiers of tail development in mice heterozygous for the brachyury (T) mutation

The brachyury, or T, locus encodes a transcription factor that plays a crucial role in the early development of all animals. In the mouse, animals heterozygous for a null mutation at this locus are born with a characteristic short tail. Expressivity of the short tail phenotype is greatly affected by genetic background. As a genetic entry into the identification of genes that interact with the Brachyury locus, we have performed a QTL analysis for modifiers of this phenotype. Surprisingly, we discovered that the major modifiers uncovered all act in a sex-limited manner. We have identified two QTLs--Brm1 on Chr 9 and Brm2 on Chr 15--that act only in female offspring(N2) from female T/+ parents(F1) and are responsible together for most, or all, of the genetic variance in phenotypic expression observed between C57BL/10 and C3H/HeJ animals.