Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  3
• Reference
  J:211989 Sohrabi Y, et al., Mapping the genes for susceptibility and response to Leishmania tropica in mouse. PLoS Negl Trop Dis. 2013;7(7):e2282
• ID
  MGI:5708105

Genes

Gene	Assay Type
Ltpr3	resistance/susceptibility
Ltpr3a	resistance/susceptibility
D3Mit25
Ltpr3b	resistance/susceptibility
Ltpr3c	resistance/susceptibility
Ltpr3d	resistance/susceptibility
Ltpr3e	resistance/susceptibility
Ltpr3f	resistance/susceptibility
Ltpr3g	resistance/susceptibility
D3Mit11

Notes

• 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 3 of the CcS16/Dem mice, labeled Ltpr3, influencing control of multiple functions. Ltpr3, Leishmania tropica response 3, identified multiple peaks, D3Mit25 at 27.32 cM and D3Mit11 at 43.71 cM.
  
  02.11.2016 Curator Note: We have retained the broader QTL identified in this study as Ltpr3. We have also assigned official nomenclature to each of the independent traits that map with significance within the broader Ltpr3 locus creating Ltpr3a through Ltpr3g.
  
  Ltpr3a was identified in only the (BALB/c x CcS16)F2 mice, influencing the number of parasites in the spleen measured at week 43 after infection. Ltpr3a mapped to D3Mit25, corrected p=0.0085. The STS/A allele at Ltpr3a determined a lower parasite load and accounted for 19.38% of trait variance. [Table 2.]
  
  Ltpr3b controlled serum levels of CCL3 measured at week 7, peaking with marker D3Mit11, corrected p=0.0046 with the BALB/c allele determining higher serum levels at this locus and accounting for 4.56% of trait variance. [Table 5.]
  
  Ltpr3c was identified in interaction with Ltpr7b at D17Mit130 where it influenced CCL3 serum levels, corrected p=0.0014. This interaction accounted for 3.33% of trait variation. [Table 6.] The largest effect was seen at Ltpr3c when Ltpr7b was homozygous with the STS/A allele. In that genotypic situation the Ltpr3c CC alleles cause more than 300 times higher levels of CCL3.
  
  Ltrp3d was another main effects QTL controlling serum levels of CCL5 at D3Mit11 at week 7, corrected p=0.0010, with the BALB/c alleles associated with the higher levels. Ltpr3d accounted for 3.99% of trait variance. [Table 5.]
  
  Ltpr3e was identified in interaction with Ltpr7c at D17Mit180, influencing CCL5 serum levels at D3Mit11, corrected p=0.0012. The Ltpr3e locus with homozygous BALB/c alleles cause 28 time higher CCL5 levels when inherited with homozygous STS/A alleles at Ltpr7c. [Table 6.]
  
  Ltpr3f was a main effects QTL determining skin lesion size at D3Mit11, corrected p=0.042 when measured at 21 weeks post infection. STS/A alleles at this locus determined larger skin lesions. Ltpr3f accounts for 12.48% of trait variance. [Table 1.]
  
  Ltpr3g at D3Mit11 was identified in interaction with Ltpr2f at week 43 after infection at D2Mit257, corrected p=0.0010. F2 mice with homozygous STS/A alleles at both Ltpr3g and Ltpr2f have the smallest splenomegaly. This interaction accounted for 9.05% of trait variance. [Table 3.]