NOD.129S4(B6)-Rel^tm1Hcl/PramJ

Stock number: 035009
Product name: NOD.c-Rel^-
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

NOD.c-Rel^- mice carry a Rel (reticuloendotheliosis oncogene or c-Rel) KO on the diabetes-susceptible NOD/ShiLtJ background. Homozygotes develop accelerated insulitis, hyperglycemia and diabetes. This strain may be useful for studies of the Rel oncogene and autoimmunity

Detailed description

Rel (reticuloendotheliosis oncogene or c-Rel) is a member of the NFKB/Rel transcription factor family and is involved in the regulation of cytokine expression in T cells and in the regulation multiple autoimmune and inflammatory diseases. Rel- is a knockout (KO) allele with the neomycin resistance cassette replacing exon 5. In NOD.c-Rel- mice, Rel has been introgressed into the diabetes susceptible NOD/ShiLtJ background. Homozygous mice are viable and fertile, however diabetes onset in females begins as early as 9 weeks of age, with 100% of homozygotes and 80% of heterozygotes diabetic by 17-18 weeks of age. Males are less susceptible to diabetes with an 50-60% incidence, some males develop hyperglycemia as early as 10-15 weeks (under SPF conditions). Homozygotes exhibit an 80% decrease in CD4+ Treg cells in the thymus (75% in spleen), a reduction in anti-CD3/CD28-induced expression of the Th1 cytokines (IL2, IFNG and GM-CSF) from both CD4+ and CD8+ T cells, as well as accelerated insulitis, hyperglycemia and diabetes development. Heterozygotes develop an intermediate phenotype. This strain may be useful for studies of the Rel oncogene and autoimmunity.

Of note, B6.c-Rel- mice on a congenic C57BL/6J background are available as Stock No. 039712.

Development

A targeting vector containing a neomycin resistance cassette was used to replace exon 5 of the Rel (reticuloendotheliosis oncogene or c-Rel) gene. The targeted region includes nucleotides encoding amino acids 102-130. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 females and the colony was maintained on a mixed background. Western blot analysis of spleen, thymus and lungs confirms that protein is not expressed. Dr. Parameswaran Ramakrishnan of Case Western University obtained mice from Dr. Hsiou-Chi Liou (Cornell University) and introgressed the allele into diabetes-susceptible NOD mice using a speed congenic approach (The Jackson Laboratory). Upon arrival, mice were bred to NOD/ShiLtJ (Stock No. 001976) for at least one generation to establish the colony.

Allele

Symbol: Rel^tm1Hcl
Name: targeted mutation 1, Hsiou-Chi Liou
MGI accession ID: MGI:2180672
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: c-Rel-
Marker symbol: Rel
Marker name: reticuloendotheliosis oncogene
Marker synonyms: c-Rel; HIVEN86A; IMD92
Chromosome: 11
Strain of origin: 129S4/SvJae
Molecular note: Exon 5 (which encodes amino acids 102-130) was replaced with a neomycin resistance gene via homologous recombination. Western blot assay of spleen lysates from homozygous mutant animals verified the absence of gene expression.