DR3+/- Mouse

Gene/Protein Targets

DR3 (Death domain-containing Tumour Necrosis Factor Receptor family member).

Relevance: In vivo study of DR3-induced apoptosis & DR3 function; in vivo study of negative T cell selection & development.
Model Type: Knockout Models
Genetic Background: C57BL/6
Zygosity: Heterozygous
Phenotype Keywords: Immune / lymphatic abnormalities
Disease Keywords:
Production Details:

A DR3 targeting vector, replacing the entire DR3 coding region with a loxP flanked resistance cassette, was transfected into GK129 ES cells. Correctly targeted ES cells, containing a homologous recombination event, were injected into C57BL/6 blastocysts. Chimeric offspring were mated to C57BL/6 mice to yield mice heterozygous for the mutant allele.

References:

Wang et al. 2001. Molecular and Cellular Biology. 21:3451-61. PMID: 11313471Read more

Notes:

The DR3-/- mouse exhibits complete knockout of DR3, a death domain-containing tumour necrosis factor receptor. which mediates one of the key regulators of the cell division cycle. Negative selection and anti-CD3-induced apoptosis are significantly impaired in DR3-null mice. In contrast, both superantigen-induced negative selection and positive selection are normal. The pre-T-cell receptor-mediated checkpoint, which is dependent on TNFR signaling, is also unaffected in DR3-deficient mice. These data reveal a nonredundant in vivo role for this TNF receptor family member in the removal of self-reactive T cells in the thymus.