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. 1996 Oct 29;93(22):12467–12472. doi: 10.1073/pnas.93.22.12467

Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses.

J D Gorham 1, M L Güler 1, R G Steen 1, A J Mackey 1, M J Daly 1, K Frederick 1, W F Dietrich 1, K M Murphy 1
PMCID: PMC38015  PMID: 8901605

Abstract

Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring Th1 development and others (e.g., BALB/c) favoring Th2 development. Recently we found that B10.D2 exhibit an intrinsically greater capacity to maintain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity to undergo IL-12-induced Th1 development. To begin identification of the loci controlling this genetic effect, we used a T-cell antigen receptor-transgenic system for in vitro analysis of intercrosses between BALB/c and B10.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefore the subsequent Th1/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with elevated serum IgE levels, suggesting that genetic control of Th1/Th2 differentiation in mouse, and of atopy development in humans, may be expressed through similar mechanisms.

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Selected References

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