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.
In analysis of both the (BALB/c x CcS16)F2 mice and the (CcS16 x BALB/c)F2 mice, the authors identify a locus on Chr 4 of the CcS16/Dem mice, labeled Ltpr4, influencing control of multiple functions. Ltpr4, Leishmania tropica response 4, maps to Chr 4 of Ccs16 with marker D4Mit153.
02.11.2016 Curator Note: We have retained the broader QTL identified in this study as Ltpr4. We have also assigned official nomenclature to each of the independent traits that map with significance within the broader Ltpr4 locus creating Ltpr4a, Ltpr4b and Ltpr4c.
Ltpr4a at D4Mit153, corrected p=0.077, measured at 19 weeks after infection influenced skin lesion size. The STS/A allele at this locus was associated with smaller lesions. Ltpr4a accounted for 9.66% of trait variance. [Table 1.]
Ltpr4b, also peaking with marker D4Mit153, was detected in interaction with Ltpr1 at D2Mit156 measured at week 43, corrected p=0.032. Highest parasite numbers in inguinal lymph nodes were observed in F2 mice with homozygous STS/A alleles at Ltpr4b and homozygous BALB/c alleles at Ltpr1. This interaction explained 7.31% of trait variance. [Table 4.]
Ltpr4c, also peaking at D4Mit153, was detected in interaction with Ltpr8d at D18Mit40 controlling parasite numbers detected in liver at 43 weeks after infection, corrected p=0.021. Explaining 8.11% of trait variance. [Table 4.] F2 mice with homozygous BALB/c alleles at Ltprc4 and heterozygous alleles at Ltpr8d had the highest parasite burden in liver.
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