A novel putative transporter maps to the osteosclerosis (oc) mutation and is not expressed in the oc mutant mouse

The phenotype of mice homozygous for the osteosclerosis (oc) mutation inclu des osteopetrosis, and a variety of studies demonstrate that osteoclasts in these mice are present but nonfunctional. We have identified a novel gene that has homology to a family of la-transmembrane domain proteins with tran sport functions and maps to proximal mouse chromosome 19, in a region to wh ich the oc mutation has been previously assigned. The putative transporter is abundant in normal kidney, but its expression is markedly reduced in kid neys from oc/oc mice when tested using Northern and Western analyses. South ern analysis of this gene, which we call Roct (reduced in oc transporter), demonstrates that it is intact and unrearranged in oc/oc mice. In situ stud ies show that Roct is expressed in developing bone. We propose that the abs ence of Roct expression results in an osteopetrosis phenotype in mice. (C) 1999 Academic Press.