MOUSE RUMP-WHITE MUTATION ASSOCIATED WITH AN INVERSION OF CHROMOSOME-5

The rump-white (Rw) mutation in the mouse was previously mapped as par t of a cluster of spotting genes on Chromosome (Chr) 5 that includes t he dominant spotting (W) and patch (Ph) loci. Recent studies have show n that the W locus encodes the KIT tyrosine kinase cell surface recept or and that Ph is a deletional mutation encompassing the platelet-deri ved growth factor receptor alpha subunit (Pdgfra) gene. However, the m olecular basis of the Rw mutation remains to be established. We have a nalyzed an interspecific Mus spretus backcross segregating Rw and seve ral loci proximal and distal to the W/Ph/Rw region to study the basis of this mutation. These studies indicated that loci within the En2 to Kit region of the chromosome do not recombine with one another even th ough they have been separated in other mapping studies presented here and elsewhere. We conducted a series of fluorescent in situ hybridizat ion (FISH) studies with genomic probes to En2, Msx1, D5Buc1, and Kit t o compare the physical order of these loci on the Rw and wild-type chr omosomes. The Kit locus mapped to approximately the same region on bot h chromosomes of the Rw heterozygotes, while the positions of En2, Msx 1, and D5Buc1 were reversed on the two chromosomes. Taken together, bo th the genetic and physical mapping data establish that the Rw mutatio n is associated with an inversion involving loci in the proximal regio n of Chromosome 5.