Experiment
L. tropica causes cutaneous leishmaniasis in humans and it can also visceralize. Experiments with mice revealed that manifestations of the disease after infection with L. tropica were strongly influenced by the geneotype of the host.
Mice from recombinant congenic strain CcS16, derived from a BALB/c-c-STS/A (CcS/Dem) panel, were crossed with BALB/c mice to create two experimental groups. The CcS16 strain carries 12.5% genes from the resistant parental STS/A strain and 87.5% from the susceptible BALB/c strain and is more susceptible to L. tropica than BALB/c mice. CcS16 was in more than 90 generations of inbreeding when used for these experiments.
The first experiment consisted of 111 mice, 51 mice from a (BALB/c x CcS16)F2 cross and 60 mice from the recprical cross, (CcS16 x BALB/c)F2. The second group contained a total of 134 mice, 64 from a (BALB/c x CcS16)F2 cross and 70 mice from the (CcS16 x BALB/c)F2 cross. Both F2 hybrid groups were derived from the same F1 parents. Infected mice from both experimental groups were genotyped and their linkage with pathological symptoms and systemic immune responses were determined, revealing eight Ltrp (Leishmania tropica response) loci. These loci are functionally heterogeneous - each influences a different set of responses to the pathogen.
Analyzing both the (BALB/c x CcS16)F2 mice and the (CcS16 x BALB/c)F2 mice, loci Ltpr1, Leishmania tropica response 1 and Ltpr4b, Leishmania tropica response 4b, were detected in gene-to-gene interactions. Parasite numbers in inguinal lymph nodes were influenced by interaction between Ltpr1, linked to D2Mit156 at 31.66 cM and Ltpr4 linked to D4Mit153 at 44.59 cM (corrected p=0.0046). [Table 4.]
Highest parasite load was observed in F2 mice with homozygous STS/A alleles at Ltpr4 and homozygous BALB/c alleles ar Ltpr1. The interaction accounted for 7.31% of trait variance.
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