Genetic control of BCG-induced granulomatous inflammation in mice

The genetics of BCG-induced pulmonary granulomatous inflammation (PGI) and splenomegaly was studied by breeding experiments and by the use of BXD recombinant inbred (RI) and allotype-congenic mice. Breeding studies indicated that the genetic control was multifactorial; this observation was confirmed using BXD RI mice. In addition, studies with BXD RI mice suggested that genes linked to the Igh complex influence responsiveness. The influence of the Igh-linked genes was studied further using allotype-congenic mice; SJL mice (Ighb) developed significantly greater PGI than their congenic partner, SJA/9 (Igha). Data from BALB.Igb, CB-20, and BAB-14 mice suggested that Igh-linked genes influencing PGI were a considerable distance from Igh-1. Igh-linked genes that influence BCG-induced splenomegaly were located on the centrometric side of the Igh-1 locus. This was shown by data in which splenomegaly in BALB.Igb and CB-20, but not BAB-14, mice was significantly augmented over BALB/c mice. Further studies are necessary to understand the significance of these observations.