Genetic Control of BCG-Induced Granulomatous Inflammation in Mice

Abstract

The genetics of BCG-induced pulmonary granulomatous inflammation (PGI) and splenomegaly was studied by breeding experiments and by the use of BXD recombinant inbred (Rl) and allotype-congenic mice. Breeding studies indicated that the genetic control was multifactorial; this observation was confirmed using BXD Rl mice. In addition, studies with BXD Rl mice suggested that genes linked to the Igh complex influence responsiveness. The influence of the lgh-linked genes was studied further using allotype-congenic mice; SJL mice (Igh_b) developed significantly greater PGI than their congenic partner, SJA/9 (Igh^a). Data from BALB.lg, CB-20, and BAB-14 mice suggested that lgh-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.Ig^b and CB-20, but not BAB-14, mice was significantly augmented over BALBIc mice. Further studies are necessary to understand the significance of these observations.