Mice homozygous for Il4tm1Cgn have a reduced ability to produce Th2-derived cytokines. IL4 deficient NOD mice develop IDDM with the same incidence as standard NOD/Lt controls.
Dr. David Serreze, The Jackson Laboratory
Complete Freund's adjuvant (CFA) induced suppression of diabetes in NOD mice has been associated with a shift to Th2 cytokine production. NOD mice deficient in IL4 were created to investigate the role of IL4 in this shift. Mice homozygous for the Il4tm1Cgn targeted mutation are viable and fertile. T and B cell development is normal but IgG1and IgE levels and the ability of homozygous mutant mice to produce Th2-derived cytokines are significantly reduced. IL4 deficient NOD mice develop IDDM with the same incidence as standard NOD/Lt controls, and there is no change between IL4 deficient and wildtype NOD in disease protection conferred by treatment of bacillus Calmette-Guerin vaccine (BCG) or CFA. Both IL4 deficient and wildtype NOD mice are significantly protected from insulitis by treatment of CFA but not by treatment of BCG. (Serreze et al 2001)
A 4.5 kb targeting vector containing the first two exons of the Il4 gene and a neomycin resistance cassette was used to disrupt the first exon of Il4. This construct was transfected into E14-1 embryonic stem cells (derived from 129P2/OlaHsd). Correctly targeted ES cells were injected into C57BL/6 blastocysts. The mutation was maintained on a B6;129 segregating background until it was congenically transferred to NOD/Lt using a marker assisted protocol. At the sixth backcross generation, mice heterozygous for the Il4tm1Cgn mutation and homozygous for all insulin dependent diabetes susceptibility loci (Idd) were intercrossed to produce mice homozygous for the mutation and all Idds. This strain is maintained by sibling mating homozygotes. (Kuhn et al., 1991; Serreze et al., 2001.)
|Allele Name||targeted mutation 1, University of Cologne|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IL-4-; IL-4 KO; IL4-; IL4tm1cgn129; IL-4KO; IL4T; IL-4T-|
|Gene Symbol and Name||Il4, interleukin 4|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A translational stop codon and a neomycin resistance gene were inserted into the first exon of the gene.|
|Mutations Made By|| |
Dr. Ralf Kuhn, Max-Delbrück Center for Molecular Medicine
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