NOD.129S2(B6)-Cd8a^tm1Mak/DvsJ

Stock number: 005513
Product name: NOD.CD8a^null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

Homozygotes of these Cd8a knock-out mice are deficient in functional cytotoxic T-cells.

Detailed description

Mice homozygous for the Cd8a^tm1Mak targeted mutation are deficient in functional cytotoxic T-cells; however helper T-cell development and function is comparable to normal. NOD.129S2(B6)-Cd8a^tm1Mak/DvsJ mice are homozygous for linkage markers delineating all known Idd loci of NOD origin and strongly diabetes resistant (1/17 females are diabetic by 30 weeks of age). Survival of allogeneic skin grafts in NOD.129S2(B6)-Cd8a^tm1Mak/DvsJ mice treated with an anti-Cd40 ligand specific mAb and donor specific transfusion (DST) is significantly shorter (MST=21days) than in B6.129S2-Cd8a^tm1Mak/J (MST=101days) and (NODXB6)F1-Cd8a^tm1Mak (MST=35days) mice. Homozygous mutant mice are strongly, but not completely diabetes resistant (<3% in females) and insulitis is strongly, but not completely repressed.

This model is useful for sorting out the genetic mechanism(s) involved in transplant tolerance and for studying the role of Cd8a in diabetes research.

Development

Using marker assisted analysis for all known Idd loci, B6.129S2-Cd8a^tm1Mak/J at N13 from The Jackson Laboratory's Induced Mutant Resource (Stock #002665) was backcrossed to NOD/Lt for 10 generations, prior to intercrossing to generate homozygotes (Pearson et al, 2003). In 2005, NOD.129S2(B6)-Cd8a^tm1Mak/Dvs homozygous strain at N9F11 was transferred from David Serreze's research colony to the Type 1 Diabetes Resource at The Jackson Laboratory.

Allele

Symbol: Cd8a^tm1Mak
Name: targeted mutation 1, Tak Mak
MGI accession ID: MGI:1857149
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd8a
Marker name: CD8 antigen, alpha chain
Chromosome: 6
Strain of origin: 129S2/SvPas
Molecular note: A neomycin resistance gene was inserted into exon 1. Flow cytometry analysis on thymus and lymph node cells derived from homozygous mice confirmed that no detectable encoded protein was expressed on the cell surface.