International Mammalian Genome Society

F23 Cloning and Characterization of Glas-1, A Novel Gene Associated with Mouse Osteopetrosis

Mathieu Ferron, Hugues Bernard and Jean Vacher. IRCM, Montréal, Québec, Canada

Osteopetrosis is a genetic disease caused by either absence or loss of osteoclast function, a hematopoietic cell responsible for bone tissue resorption. The mouse grey-lethal (gl) mutation is a recessive osteopetrotic phenotype similar to human osteopetrosis. To identify both putative target genes of gl and osteopetrosis associated gene, we have undertaken a differential display study. By comparison of genes expression in the spleen of wild type and gl mice, we have isolated several partial cDNA donw-regulated in gl. Interestingly, one of them corresponds to the immunoglobulin J chain gene which is consistent with a reduction in B220⁺ B cell population in gl mouse spleen. A second one, which corresponds to a novel gene, have been named glas-1 for gl-associated gene. This partial cDNA was used for the screening of a 70Z3 cell line cDNA library, leading to isolation of an almost complete cDNA. Northern blot analysis indicate that glas-1 encodes a unique ~2.2 kb transcript expressed in spleen, thymus and bone marrow in wild type mouse, but down regulated in the gl mouse spleen. Further, high level of expression was detected in T, B and pre-B cell lines. A partial genomic clone was then isolated, sequenced and a 3' RFLP polymorphism, detected by a PCR assay, was identified. Segregation analysis of this polymorphism in a backcross generated from the cross (M. spretus x C57BL/6) F₁ x M. spretus localized glas-1 to mouse chromosome 13, between D13Mit9 and D13Mit8 markers. Taken together, these results suggest that glas-1 could be a potential down-stream target (direct or indirect) of gl and could be involved in lymphopoiesis.