Inheritance of Resistance of Mice to Enteric Bacterial and Neurotropic Virus Infections

Abstract

Previous studies from this laboratory have shown that certain factors regulating the resistance of mice to naturally induced Bacillus enteritidis infection are inborn (1). The new data to be presented show that, under the experimental conditions, resistance to B. enteritidis and resistance to St. Louis encephalitis virus" are inherited in a similar and relatively definite manner but independently. Materials and TechniqueThe general technique employed in this work has been described (1). It was pointed out that following early experiments on small numbers of mice from the Rockefeller Institute breeding stock, a special breeding colony was started in 1929 with 600 of these animals which were tested and proved free of infection. The diet was changed from a bread and milk ration, producing mortalities following injection of mouse typhoid bacilli generally high (70 per cent), but fluctuating with season, to one producing low and more stable mortalities (37 ± 1.6 per cent).Finally, B. enteritidis rather than B. aertrycke was used as the test agent. These different experimental conditions, reflected in the different levels of mortality of the two control groups, permit early and later data to be compared'qualitatively (1) but not ~luantitatively (Hill, 2).The breeding stock was established and has remained free of the infections under investigation and others as determined by continued testing. At the outset it would have been preferable in selecting for possible resistant strains to proceed as with the susceptibles and choose for breeding, unexposed siblings of tested litters rather than the survivors themselves. This error was committed on but a single occasion, at the commencement of the experiment, however, and the rigid measures employed for detecting infected animals were known to be effective. Only the uninfected survivors were mated and the resulting litters tested, found to be uninfected, and then placed in the breeding room. Subsequently, no survivors have been used for breeding.The mouse colony is subjected to continued search for infectious agents. The occasional sickly mouse is sacrificed and tested for the presence of pathogenic 261

Rôle of Inborn Resistance Factors in Mouse Populations Infected With Bacillus Enteritidis

“…In reply we argue that the extreme individuals are in reality closely related both to one another and to the moderately susceptible individuals (2). In some cases the relation is that of siblings--in all events, the differences are those which may occur normally among individuals of the same family.…”

Nutrition of the Host and Natural Resistance to Infection

“…These stocks are maintained free of Salmonella infection. The derivation of these strains has been described by Webster (4,5). Briefly, they are characterized by the four possible combinations of relative resistance and susceptibility to a bacterial disease (mouse typhoid, salmonellosis), and to a virus disease (St. Louis encephalitis); v/z., bacteria-resistant, virus-resistant; bacteria-susceptible, virus-resistant; bacteria-resistant, virus-susceptible; and bacteria-susceptible, virus-susceptible.…”

“…The opportunity to test the double strain inoculation method as a detector of differences in natural resistance due to genetic composition of the host was made possible by the presence in our laboratory of four different inbred strains of mice, the descendants of Webster's selected stocks (4,5), which differed widely in their response to Salmonella infection, as measured by survivorship frequency. As Table I shows, two strains were "resistant" and two "susceptible."…”

“…These divergent responses to infection were arranged by the geneticist's operation of inbreeding and selection, the guide to selection, be it noted, having been the response to an infection test performed with a single culture of Salmonella. The differences between these strains have been established as being innately, or genetically, determined (5). Indeed, the very fact that such stocks exist has been regarded by Zinsser, Enders, and Fothergill (7) as "the most trustworthy evidence which we possess at present for regarding it (inherited resistance) as a real phenomenon.…”

“…Although these facts may make permissible the use of the double strain inoculation test in studies of natural resistance, is this test a compulsory one? It would not appear to be so, for in Webster's hands (4,5) a single culture of Salmonella enteritidis served satisfactorily for the selection of naturally resistant and susceptible mice. An explanation for this may be that Webster's cultures were not homogeneous, but heterogeneous and hence are not logically considered as single cultures, but as mixtures containing, in all probability, both virulent and avirulent ceils.…”