Trypanosoma rhodesiense: analysis of the genetic control of resistance among mice

Abstract

Inbred mouse strains differ in their resistance to infection with the human pathogen Trypanosoma rhodesiense. Of the strains tested, C57BL/6 (B6) mice were the most resistant, and BALB/c (C) mice were among the most susceptible. The genetic basis underlying the different susceptibility of these two strains was analyzed. (CXB6)F1 progeny of either sex were more resistant than the BALB/c parent. Also, the backcross of F1 mice to the susceptible male or female BALB/c parent resulted in 52.0% susceptible (i.e., death on or before day 24) progeny, as compared with only 0.64% susceptible F1 progeny. The data suggested that resistance was the dominant phenotype and that the resistant allele was carried by the B6 parent. The presence of another locus regulating resistance to death was suggested by the facts that only a small percentage of F2 mice were susceptible and that a number of F1 and F2 mice were more resistant than their B6 parent. The locus responsible for these phenomena was presumably hypostatic in nature and carried by BALB/c mice, and its effects were only evident in the presence of other resistance genes. In addition, the observation that many of the susceptible individuals among F2 and backcross mice were more resistant than the BALB/c mice suggested that other minor genes also modulated the response of mice to infection. A set of CXB recombinant inbred mice was tested as well, and the individual strains within this set could also be placed into four groups: susceptible, intermediate, resistant, or hyperresistant. These findings are compatible with the multigenic model suggested by the Mendelian analyses.