UROGENITAL SYNDROME (US) - A DEVELOPMENTAL MUTATION ON CHROMOSOME-2 OF THE MOUSE

Urogenital syndrome (us) is a recessive mutation in mice characterized primarily by abnormalities of the axial skeleton and urogenital organ s. We established linkage of us with the centromeric end of Chromosome (Chr) 2, using the Robertsonian Chr Rb(2.8)2Lub. Analysis of progeny from crosses using the Chr 2 markers Danforth's short tail (Sd) and ul naless (Ul) positioned us near two loci that have recently been mapped by RFLPs, nonerythroid alpha-spectrin (Spna-2) and the paired-box-con taining-gene-8 (Pax-8). The position of us relative to these loci was established by analysis of progeny from interspecific backcrosses betw een the us strains and Mus spretus. The estimated map distances and mo st likely gene order are centromere-Pax-8-2.1 +/- 1.2-us-0.7 +/- 0.7-S pna-2; however, the reverse order cannot be ruled out. Our data make i t unlikely that us is a mutation in either Spna-2 or Pax-8. Spna-2 is close enough to us, however, to be a useful marker for positional clon ing of the us gene. The human mutation Nail-patella-syndrome (NPS1) ma ps to the region of human Chr 9 (9q34) that is homologous to the us re gion of mouse Chr 2. Phenotypic similarities between the two syndromes suggest the possibility that they are caused by mutations at homologo us loci.