International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr. Marie LipoldovŠ
Institute of Molecular Genetics
Fleming. nam. 2
Prague 166 37
Czech Republic

Co-Authors: 2)SvobodovŠ M., 1)HavelkovŠ H., 1)BadalovŠ J., 1)Vladimirov V. 1)VojtiökovŠ J. 1)KrulovŠ M. 2)Volf P. 3)Demant P.
Institutions: (1) Inst. Molec. Genetics, (2) Charles University, (3) The Netherlands Cancer Institute

The progress of the human genome project has awakened interest in the genes with low penetrance that influence† multigenically controlled diseases. Infection by Leishmania major in the mouse is† suitable to assess the extent to which heterogeneity of a complex disease can be revealed by total genome dissection, as its outcome† depends considerably on the hosts' inherited capacity to control the parasite. Progression or resolution of the disease has been attributed to† a predominant Th2 response or Th1 response, respectively. We used the series of 20 CcS/Dem recombinant congenic strains, each of which carries a different random portion of 12.5% genes of the donor resistant strain STS/A† on the genetic background of the susceptible strain BALB/cHeA. The CcS/Dem strains differed considerably in their immune responses and pathology, and the disease or healing has been in different CcS/Dem strains associated with various†† components of Th response. We integrated the genetic linkage study of susceptibility with determination of several symptoms of disease and mapped† loci Lmr3-7 controlling response to L. major† in† the most resistant strain CcS-5, each apparently associated with a different combination of pathological symptoms and immunological reactions.† Analysis of (BALB/c x CcS-16)F2 and (BALB/c x CcS-20)F2 mice revealed† that two of them, Lmr5 and Lmr3 control L. major response also in the strains CcS-16† and -20, respectively, in combination with additional Lmr loci.

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