Ctla4 (cytotoxic T-lymphocyte-associated protein 4) knockout out mice die by 3-4 weeks of age following an accumulation of T cell blasts, which infiltrate spleen, lymph nodes,liver, heart, lung, bone marrow and pancreas. These mice may be useful for studies of the negative regulation of T cell activation and lymphocyte homeostasis.
Dr. Tak Mak, University Health Network/Un of Toronto
The Ctla4 (cytotoxic T-lymphocyte-associated protein 4) gene is a member of the immunoglobulin superfamily and encodes a homolog of the E. coli mismatch repair gene mutS. Ctla4 is involved in the regulation of T cell activation. Mice homozygous for the knockout allele are born at the expected Mendelian frequency and are healthy at birth. By 2 weeks of age they sicken and do not live beyond 4 weeks of age. Death is a result of myocardial infarction. Lymph nodes and spleens exhibit an accumulation of T cell blasts as well as an up-regulation of activation markers. Blast cells infiltrate liver, heart, lung, bone marrow and pancreas. Serum immunoglobulin levels of all subtypes are elevated and an expanded population of activated B cells is observed. These mice may be useful for studies of the negative regulation of T cell activation and lymphocyte homeostasis.
|Allele Name||targeted mutation 1, Tak W Mak|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ctla4, cytotoxic T-lymphocyte-associated protein 4|
|Strain of Origin||129P2/OlaHsd|
|General Note||Homozygous mutant mice accumulate T cell blasts in the lymph nodes and spleens which also infiltrate liver, heart, lung, and pancreas. Serum immunoglobulin is elevated, and the mice die by 3 to 4 weeks old. T cells proliferate when stimulated via T cell receptors, but are liable to Fas induced apoptosis (J:29652).|
|Molecular Note||A neomycin selection gene replaced exon 2 and the 5' portion of exon 3. A lack of expression in homozygous mutant mice was demonstrated via fluorescence-activated cell sorting (FACS) analysis.|
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation do live beyond 3-4 weeks of age.
When using the Ctla-4- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #42058 in your Materials and Methods section.