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Faithful expression of the human 5q31 cytokine cluster in transgenic mice.
Lacy DA; Wang ZE; Symula DJ; McArthur CJ; Rubin EM; Frazer KA; Locksley
July 30, 2000
J Immunol. 2000 May 1;164(9):4569-74. Unique Identifier : AIDSLINE

Interleukins -4, -5, and -13, cardinal cytokines produced by Th2 cells, are coordinately expressed and clustered in 150-kb syntenic regions on mouse chromosome 11 and human chromosome 5q31. We analyzed two sets of human yeast artificial chromosome transgenic mice that contained the 5q31 cytokines to assess whether conserved sequences required for their coordinate and cell-specific regulation are contained within the cytokine cluster itself. Human IL-4, IL-13, and IL-5 were expressed under Th2, but not Th1, conditions in vitro. Each of these cytokines was produced during infection with Nippostrongylus brasiliensis, a Th2-inducing stimulus, and human IL-4 was generated after activation of NK T cells in vivo. Consistently fewer cells produced the endogenous mouse cytokines in transgenic than in control mice, suggesting competition for stable expression between the mouse and human genes. These data imply the existence of both conserved trans-activating factors and cis-regulatory elements that underlie the coordinate expression and lineage specificity of the type 2 cytokine genes in lymphocytes.

JOURNAL ARTICLE Animal Cell Differentiation/GENETICS/IMMUNOLOGY Chromosomes, Human, Pair 5/GENETICS/*IMMUNOLOGY Cytokines/ADMINISTRATION & DOSAGE/*BIOSYNTHESIS/*GENETICS/ PHYSIOLOGY Gene Expression Regulation/*IMMUNOLOGY Human Interleukin-4/BIOSYNTHESIS Intracellular Fluid/IMMUNOLOGY/METABOLISM Killer Cells, Natural/IMMUNOLOGY/METABOLISM Lymphocyte Subsets/CYTOLOGY/IMMUNOLOGY/METABOLISM Mice Mice, Inbred BALB C Mice, Transgenic Microinjections *Multigene Family Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes, Helper-Inducer/CYTOLOGY/IMMUNOLOGY Th2 Cells/IMMUNOLOGY/METABOLISM Transgenes/*IMMUNOLOGY