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.
Ltpr6, Leishmania tropica response 6, was identified as a significant locus in only the (BALB/c x CcS16)F2 mice. It mapped as a main effects QTL to Chr 11 with D11Mit37 and was identified as significant in an interaction with Ltpr2g.
02.17.2016 Curator Note: We have retained the broader QTL identified in this study as Ltpr6. We have also assigned official nomenclature to each of the independent traits that map with significance within the broader Ltpr6 locus creating Ltpr6a and Ltpr6b.
Ltpr6a, was identified as a main effects QTL mapping to Chr 11 with peak marker, D11Mit37 at 49.70 cM, corrected p=0.014, at 43 weeks after infection. The STS/A allele at this locus was associated with higher pararsite numbers in the spleen. It accounted for 29.58% of trait variation. [Table 2.]
Ltpr6b at D11Mit37 was identified in interaction with Ltpr2g at D2Mit257 when measured at week 7, corrected p=0.016. The highest CCL7 levels were observed in STS/A homozygous alleles at Ltpr6b in combination with heterozygous (CS) or homozygous STS/A at Ltpr2g. This interaction accounted for 6.66% of trait varaince.[Table 6].
Analysis Tools