title: Different genetic control of cutaneous and visceral disease after Leishmania major infection in mice.
abstract: The mouse strains BALB/cHeA (BALB/c) and STS/A (STS) are susceptible and resistant to Leishmania major-induced disease, respectively. We analyzed this difference using recombinant congenic (RC) BALB/c-c-STS/Dem (CcS/Dem) strains that carry different random subsets of 12.5% genes of the strain STS in a BALB/c background. Previously, testing the resistant strain CcS-5, we found five novel Lmr (Leishmania major response) loci, each associated with a different combination of pathological and immunological reactions. Here we analyze the response of RC strain CcS-16, which is even more susceptible to L. major than BALB/c. In the (CcS-16 x BALB/c)F(2) hybrids we mapped three novel loci that influence cutaneous or visceral pathology. Lmr14 (chromosome 2) controls splenomegaly and hepatomegaly. On the other hand Lmr15 (chromosome 11) determines hepatomegaly only, and Lmr13 (chromosome 18) determines skin lesions only. These data confirm the complex control of L. major-induced pathology, where cutaneous and visceral pathology are controlled by different combinations of genes. It indicates organ-specific control of antiparasite responses. The definition of genes controlling these responses will permit a better understanding of pathways and genetic diversity underlying the different disease phenotypes.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Fleming, nám. 2, 166 37 Prague 6, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vladimirov
authors.forename: Jana
authors.initials: J
authors.lastname: Badalová
authors.forename: Milena
authors.initials: M
authors.lastname: Svobodová
authors.forename: Helena
authors.initials: H
authors.lastname: Havelková
authors.forename: Augustinus A M
authors.initials: AA
authors.lastname: Hart
authors.forename: Hana
authors.initials: H
authors.lastname: Blazková
authors.forename: Peter
authors.initials: P
authors.lastname: Demant
authors.forename: Marie
authors.initials: M
authors.lastname: Lipoldová
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006529:Hepatomegaly; D018320:Leishmania major / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D007898:Leishmaniasis, Visceral / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics; D013163:Splenomegaly