LOCALIZATION OF THE GENE RESPONSIBLE FOR THE OP (OSTEOPETROTIC) DEFECT IN RATS ON CHROMOSOME-10

Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of indep endent single gene mutations that affect osteoclast differentiation an d/or function. The osteopetrotic defect, op, is one of four spontaneou s, nonallelic mutations in rats that result in osteopetrosis. In inter cross progeny of (BN/SsN x LEW/SsN.+/op) F1 carriers, we mapped this l ocus by linkage analysis with microsatellite markers to rat chromosome 10, The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy cha in [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin] -1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], eryt hroblastic leukemia avian viral oncogene homolog-2, and proline-rich p rotein). The markers for these loci include nine not previously report ed. The op Locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its locatio n, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may p ermit a positional cloning strategy to be undertaken to identify the g ene and mutation underlying the op defect.