International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Ms Colleen Elso
Walter and Eliza Hall Institute
Post Office
Royal Melbourne Hospital
Melbourne 3050

Co-Authors:  Roberts L, Handman E, and Foote S 
Institution:   Walter and Eliza Hall Institute of Medical Research

The genetics of host response to leishmania major

Interactions between the host and the parasite are important in determining the clinical outcome of parasitic infections. Leishmaniasis provides a good example of this and, using a mouse model, provides a system whereby the complex genetics of this interaction can be explored. When infected with L. major, C57BL/6 mice develop a small cutaneous lesion but rapidly cure, whereas BALB/c mice develop a progressively expanding lesion and will die of systemic infection. Interestingly, the clinical outcome is associated with a difference in immune response between the two strains, with C57BL/6 mice mounting an early Th1 response and BALB/c a Th2 response. By determining the genetic basis of the clinical aspects of the disease, it is hoped that we will learn something about the early events leading to the establishment of Th1 and Th2 type immune responses and/or how these relate to the disease.

QTL analysis previously identified three loci linked to the average lesion score for week 3-14 post infection, a measure of disease progression in the infected host.

Current work centres on congenic mice which have been bred to determine the role each locus is playing in the disease. The results from a challenge of these mice confirms the mapping results. These mice will facilitate fine mapping to find the genes involved. Further work includes functional studies of the congenic mice in the hope of elucidating the functions and interactions of the products of these genes.

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