EVALUATION OF LAMA5 AS A CANDIDATE FOR THE MOUSE RAGGED (RA) MUTATION

The laminin alpha 5 chain is a component of the basement membranes of many developing and adult tissues. The mouse laminin alpha 5 chain gen e (Lama5) has been mapped close to the locus of the semidominant ragge d (Ra) mutation on distal chromosome 2. The cause of the Ra mutation, which is usually lethal in the homozygous state, has not been determin ed. We have investigated whether a defect in Lama5 is responsible for the ragged mutation, using the Ra-J strain. No differences in the leve l of the laminin alpha 5 chain transcript were found in placental RNA from homozygous Ra-J mutant embryos compared to normal littermates. An tiserum raised against a recombinant laminin alpha 5 chain polypeptide stained the basement membranes of both normal and homozygous mutant e mbryos to a similar extent. More precise mapping of Lama5 on an inters pecific Ra backcross indicated that Lama5 is proximal to the Ra locus. These results exclude Lama5 as a candidate gene for the Ra mutation. (C) 1998 Academic Press.