The mouse severe combined immune deficiency (scid) mutation is closely linked to the B-cell-specific developmental genes VpreB and lambda 5.

The mouse severe combined immune deficiency (scid) phenotype is due to a recessive, autosomal mutation which results in failed development of lymphocytes. An important step during normal lymphocyte development is the germline rearrangement of DNA segments to assemble functional immunoglobulin or T cell receptor genes. scid lymphocytes fail to rearrange these genes properly, resulting in the absence of mature B and T lymphocytes. This mutation was originally mapped to chromosome 16 by linkage to the immunoglobulin lambda light chain genes (Igl-1) and the coat color mutation mahoganoid. We have typed 288 progeny from backcrosses between MOLF/Ei or CAST/Ei and C.B-17-scid for the scid phenotype and nine other loci mapped to the centromeric region of MMU16. We have established a refined map of this region which places the scid gene between Prm-2 and Igl-1. In addition, no recombinations were found between scid and three other loci, VpreB, lambda 5, and D16Mit31, providing markers useful for isolating the scid gene by positional cloning.

Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

The gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) has been proposed recently as a candidate gene for the mouse severe combined immune deficiency (scid) locus. We have used a partial cDNA clone for human DNA-PKcs to map the mouse homologue using a large interspecific backcross panel. We found that the mouse gene for DNA-PKcs does not recombine with scid, consistent with the hypothesis that scid is a mutation in the mouse gene for DNA-PKcs.