Molecular genetics of androgen-inducible RP2 gene transcription in the mouse kidney

Androgen control of the RP2 gene in the mouse kidney has been modified during evolution. In inbred mice (Mus domesticus), the concentrations of mRNAs encoded by RP2 undergo a 10- to 12-fold induction in response to testosterone; in other Mus species (e.g., Mus hortulanus and Mus caroli), induction ranges from none to about two- to fourfold. In this communication, we show that androgens induced RP2 transcription in M. domesticus, although this induction may not have fully accounted for the increase in mRNA levels. Reduced mRNA inducibility in M. hortulanus and in several other species was associated with an absence of transcriptional induction. Analysis of an interspecies backcross population indicated that the difference in RP2 inducibility between M. domesticus and M. hortulanus was due to a single Mendelian locus tightly linked (0 of 47 recombinants) to RP2. The RP2 gene was found to contain at least two promoters, only one of which was highly sensitive to testosterone. These results indicate that induction of the RP2 mRNAs, as well as interspecies variations in RP2 inducibility, are primarily a consequence of effects on this promoter.