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Publication : Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice.

First Author  Fierer J Year  1999
Journal  Infect Immun Volume  67
Issue  6 Pages  2916-9
PubMed ID  10338499 Mgi Jnum  J:55132
Mgi Id  MGI:1337399 Doi  10.1128/iai.67.6.2916-2919.1999
Citation  Fierer J, et al. (1999) Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice. Infect Immun 67(6):2916-9
abstractText  Coccidioidomycosis is a fungal infection that is endemic in the southwestern United States. Infection is more severe in blacks and Filipinos, which suggests that there is a genetic basis for susceptibility to this infection in humans. We found that there is also a difference in resistance to Coccidioides immitis infection among inbred mouse strains: B6 mice are susceptible, while DBA/2 mice are resistant (T. N. Kirkland and J. Fierer, Infect. Immun. 40:912-916, 1983). In this paper we report the results of our efforts to map the genes responsible for resistance to this infection in mice. Mice were infected by intraperitoneal inoculation, and 15 days later the numbers of viable fungi in their lungs and spleens were enumerated. We also determined the amounts of interleukin-10 mRNA made in the infected lungs. These three phenotypes were mapped as quantitative traits by using the 26 available lines of recombinant inbred mice derived from a cross between B6 and DBA/2 mice. The best associations were those between the regions near the Lv locus on chromosome 4 and the Tnfr1 locus on chromosome 6. We then infected backcross mice [(B6 x DBA/2) x B6] and confirmed these associations; 14 of 16 (87%) mice that were heterozygous at both Lv and Tnfr1 were resistant to infection, whereas only 4 of 16 (25%) mice that were homozygous B6 at both loci were resistant. These are the first genetic loci to be associated with susceptibility to C. immitis, but there may be additional genes involved in murine resistance to this infection.
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