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 10 of the CcS16/Dem mice, labeled Ltpr5, influencing control of multiple functions. Ltpr5, Leishmania tropica response 5 maps to Chr 10 peaking with marker D10Mit67 at 45.35 cM and with marker D10Mit103 at 73.57 cM.
02.11.2016 Curator Note: We have retained the broader QTL identified in this study as Ltpr5. We have also assigned official nomenclature to each of the independent traits that map with significance within the broader Ltpr5 locus creating Ltpr5a, Ltpr5b.
Ltpr5a, peaking with marker D10Mit67, was identified in interaction with Ltpr7a at D17Mit130 at week 43 post infection, corrected p=0.029. F2 mice with homozygous BALB/c alleles at Ltpr5a and homozygous STS/A alleles at Ltpr7a have the most severe splenomegaly of possible genotypes. This interaction explained 7.54% of trait variance [Table 3.]
Ltpr5b, peaking with marker D10Mit103, was also identified in an interaction. Ltpr5b influences splenomegaly in interaction with Ltpr8c at D18Mit49 at week 43 after infection, corrected p=0.029. This interaction explained 6.78% of trait variation.[Table 3.] F2 mice with homozygous STS/A alleles at both Ltpr5b and Ltpr8c have the smalleset splenomegaly.
[Table 3.]
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