MOLECULAR MARKERS NEAR THE MOUSE BRACHYMORPHIC (BM) GENE, WHICH AFFECTS CONNECTIVE TISSUES AND BLEEDING-TIME

Several inherited skeletal/connective tissue defects are associated wi th hemorrhagic disorders in humans. Accordingly, three mouse mutants ( brachymorphic [bm], hemimelic extra toes [Hx], and ulnaless [Ul]), wit h inherited skeletal abnormalities, were analyzed for hemorrhagic tend encies. All three had prolonged bleeding times. Platelet numbers, Size , and function, as well as common soluble plasma clotting factors, wer e not measurably affected. To further define the bm mutation, its chro mosomal location relative to 19 other molecular markers was determined to a high resolution in a large interspecific backcross. Several micr osatellite markers were found to be very closely linked to bm and shou ld provide useful entry points for the eventual identification of this gene by positional/candidate cloning techniques. These results sugges t that inherited skeletal abnormalities and bleeding tendencies are as sociated more frequently in both humans and animal models than is comm only recognized. Identification of these genes may reveal novel relati onships between osteogenesis and hemostasis.