STRUCTURE AND CHROMOSOMAL ASSIGNMENT OF THE MOUSE FRA-1 GENE, AND ITSEXCLUSION AS A CANDIDATE GENE FOR OC (OSTEOSCLEROSIS)

We have determined the genomic structure of the mouse fra-1 gene, whic h consists of four exons and three introns at positions also found in the other members of the fos gene family, Fra-1 is expressed rather hi ghly in the brain and testes of adult mice, and at low levels in most other tissues, Absence of c-Fos leads to significantly reduced serum s timulation of fra-1 expression in gene targeted mouse fibroblasts, dem onstrating that mitogen induction of fra-1 is partially mediated by c- Fos/AP-1. A polymorphic (CA)(n) microsatellite marker was found in int ron 2 of fra-1 and used to map the gene to the centromeric region of m ouse chromosome 19, Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene fo r oc, The segregation of fra-1 in two different crosses of mice carryi ng oc and an allelism test between oc and a targeted disruption of fra -1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.