Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10

• Published in: Journal of bone and mineral research Vol. 11; no. 12; pp. 1856 - 1861
• Main Authors: Remmers, Elaine F., Du, Ying, Ding, Yan‐Ping, Kotake, Shigeru, Ge, Lynn, Zha, Hongbin, Goldmuntz, Ellen A., Wilder, Ronald L., Hansen, Carl
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01-12-1996; American Society for Bone and Mineral Research
• Subjects: Animals; Biological and medical sciences; Chromosome Mapping; Diseases of the osteoarticular system; Female; Genetic Code; Genetic Linkage; Genetic Markers; Genotype; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Meiosis - genetics; Molecular Sequence Data; Mutation; Osteopetrosis - genetics; Rats; Rats, Inbred Lew; Genetic mapping; Vertebrata; Mammalia; Osteopetrosis; Rat; Animal; Rodentia; Diseases of the osteoarticular system; Chromosome 10; Mutation; Osteochondrodysplasia; Genetic disease
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.5650111205

Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN.+/op) F1 carriers, we mapped this locus 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 chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]‐1, vesicle‐associated membrane protein [synaptobrevin‐2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog‐2, and proline‐rich protein). The markers for these loci include nine not previously reported. 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 location, 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 permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect.