International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 209 - GENETIC DISSECTION OF COMPLEX DISEASE: LEISHMANIA MAJOR INFECTION MODEL

Lipoldová M
Institute of Molecular Genetics, Prague

Co-Authors: 2) Svobodová M, 1) Havelková H, 1,2) Badalová J, 1) Vladimirov V, 1) Vojtíšková J, 1) Blažková H, 1) Krulová M, 1) Pilčík T, 1) Krulová M, 2) Volf P, 3) Demant P
Institutions: 1) Institute of Molecular Genetics, Prague, 2) Charles University, Prague, 3) The Netherlands Cancer Institute, Amsterdam

Systematic assesment of the role of host genes in clinico-pathological and immunological manifestations of Leishmania major-induced disease in mice was performed using 20 recombinant congenic (RC) strains derived from the susceptible and resistant strains BALB/c and STS, respectively. Each RC strain of CcS/Dem series carries a different random subsets of 12.5% of genes of the strain STS on the BALB/c background. This allowed us to study the pathological and immunological characteristics of infected hosts in 20 fixed different random combinations of BALB/c and STS genes. Disease or healing in different strains occurred in association with different components of immune response – with the exception of a frequently occuring correlation between the disease and IgE levels. This shows that several patterns of the immune response may be associated with the same clinical outcome, depending on the host genotype. Linkage analysis of F2 hybrids between the strain BALB/c and the RC strains CcS-5,-16 and –20 revealed 15 novel Lmr (Leishmania major response) loci that affected the response to infection. We found that cutaneous and visceral pathology was controlled by a different combination of genes, which indicates a organ specific response to L. major. We compared the predicted effect of STS alleles of loci controlling skin lesion development, splenomegaly and serum IgE level in the individual strains of CcS/Dem series with their actual phenotype. We observed a general correlation between the predicted and observed phenotype. This suggests that when a sufficient number of loci is known, the prediction of phenotype is possible.


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