A quantitative-trait locus controlling peripheral B-cell deficiency maps to mouse Chromosome 15

Peripheral B-lymphocyte homeostasis is. determined through incompletely def ined positive and negative regulatory processes. The A/WySnJ mouse, but not the related A/J strain, has disturbed homeostasis leading to peripheral B- lymphocyte deficiency. B lymphopoeisis is normal in A/WySnJ mice, but the B cells apoptose rapidly in the periphery. This B cell-in-trinsic defect seg regated as a single locus, Bcmd. in (A/WySnJxA/J)F2 mice. Here we mapped a quantitative-trait locus (QTL) that contributes to the A/WySnJ B-cell defic iency by examining the F2 progeny of a cross between strains A/WySnJ and CA ST/Ei. In this cross, minimally 1.9 QTLs controlling peripheral B lymphocyt e deficiency segregated. The (A/WySnJxCAST/Ei)F2 mice were phenotyped for s plenic B-cell percentage and the DNA from progeny with extreme phenotypes w as used to map the QTL by the simple-sequence length polymorphism method. A genome scan showed linkage between peripheral B-cell deficiency and Chromo some (Chr) 15 markers. When closely spaced Chr 15 markers were analyzed, th e 99% confidence interval for the QTL map position extended along the entir e chromosome length. The peak lod scores >17 occured between 30 and 45 cM. We conclude that a significant QTL segregating in (A/WySnJxCAST/Ei)F2 mice resides in this middle region of Chr 15.