Mapping of caspase-2 in the rat and its exclusion as a candidate gene for lymphopenia

Caspase-2 is a member of the caspase family of cystein proteases involved in programmed cell death or apoptosis. Functional and genetic data suggest it as a candidate gene for lymphopenia (Lyp)-a susceptibility gene for rat diabetes-which is responsible for the T-cell lymphopenia in the diabetes-prone BB rat. Firstly, there is a higher frequency of apoptosis among recent thymic emigrants in the diabetes-prone BB rat than in the non-lymphopenic diabetes-resistant BB rat. Secondly, caspase-2 maps close to Tcrb on mouse Chromosome (Chr) 6, while Lyp is closely linked to Tcrb on the homologous rat Chr 4. In this paper, we report genetic fine-positioning and radiation hybrid mapping of caspase-2 in the rat. Both methods positioned caspase-2 to rat Chr 4 between markers Prss1 and D4Mit5. Since Lyp maps distally to D4Mit5, between markers D4Rat75 and Npy, we exclude caspase-2 as a candidate gene for Lyp.