Susceptibility to a mouse acquired immunodeficiency syndrome is influenced by the H-2.
The development of a mouse acquired immunodeficiency syndrome (MAIDS) induced following LP-BM5 MuLV infection depends on host genetic factors. Susceptible mice, such as C57BL/6J mice, develop a profound impairment of lymphoproliferative response to mitogens and hyperplasia of lymphoid organs and succumb to infection within 6 months. These changes do not occur in resistant mice, such as A/J mice. Resistance to MAIDS is a dominant trait since (C57BL/6J x A/J)F1 hybrid mice did not develop any immune dysfunctions following infection. Genetic regulation of the trait of resistance/susceptibility to MAIDS was determined in AXB/BXA recombinant inbred (RI) mouse strains (derived from resistant A/J and susceptible C57BL/6J progenitors). Two different criteria were used to determine their resistance or susceptibility to developing MAIDS: the gross pathologic evaluation of lymphoid organs at 13-15 weeks of infection, and survival. RI mouse strains segregated into two non-overlapping groups. The first group did not develop any significant pathology, and these mouse strains were considered as resistant to MAIDS. The second group showed the virus-induced pathological changes as well as an immunological dysfunction as seen in C57BL/6J progenitor mice, and these strains were thus considered as susceptible to MAIDS. This bimodal strain distribution pattern of resistance/susceptibility to MAIDS among the RI strains suggests that this phenotype is controlled by a single gene. Linkage analysis with other allelic markers showed a strong association between resistance/susceptibility to MAIDS and the H-2 complex. Possession of the H-2b haplotype derived from C57BL/6J mice was associated with susceptibility to MAIDS, while the H-2a haplotype conferred resistance to the disease. This finding was confirmed by demonstrating that H-2a congenics on the susceptible C57BL/10 background were as resistant to MAIDS as A/J mice which donated the H-2a locus. Gene(s) within the H-2 complex thus represent the major regulatory mechanism of resistance/susceptibility to MAIDS.
Hamelin-Bourassa
D
D
McGill Centre for the Study of the Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
Skamene
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E
Gervais
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F
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics*; D009052:Leukemia Virus, Murine; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL
D006183:H-2 Antigens