Genetic mapping of genes regulating the thymus size in back-cross rats between the laboratory BUF/Mna strain and the MITE strain derived from the wild rat, Rattus norvegicus

The thymoma prone BUF/Mna (B) rat is a useful model for studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at all stages of life. A locus, Ten-1, which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the locus, {Bx(BxMITE)F1} BC rats were generated by crossing the B strain with the inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargement were found in genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11, and D1Mlt6, by χ²-test and Student's t-test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1, in this region. Paradoxically, a suppressive locus, Tsu-1, to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT, D3Mlt16, and D3Mlt13. By analyses of MAPMAKER/EXP and MAPMAKER/QTL, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.