NOD.129P2(B6)-B2m^tm1Unc/J

Stock number: 002309
Product name: NOD β₂m KO
Research areas: Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

These B2m knock-out mice exhibit little if any MHC class I protein expression on the cell surface with deficiency in CD8⁺ cytotoxic T-cells, NK1⁺ T cells, and decreased levels of serum Ig.

Detailed description

Mice homozygous for the B2m^tm1Unc targeted mutation have little if any MHC class I protein expression on the cell surface. There are few CD8⁺ cytotoxic T-cells and under some circumstances a compensatory increase in CD4⁺ cytotoxic T-cells. Immune responses involving CD8⁺ T-cells are severely deficient providing a model to assess the role of CD8⁺ cells and class I MHC in various experimental systems. Other traits of B2M deficient mice include: NK cell deficiency, NK1⁺ T cells deficiency and decreased levels of serum Ig. Some forms of lupus autoimmunity are severely reduced. (Christianson, J Immunol 156:4932-9, 1996). Hemachromatosis has been noted in certain genetic backgrounds (Rothenberg BE, Voland JR, Proc Natl Acad Sci USA 93:1529-34, 1996). The B2m^tm1Un mutation backcrossed to the NOD/Lt strain serves as a MHC class I-negative, CD8⁺ deficient diabetes resistant stock for comparison to the NOD/LtJ strain (Stock No. 001976). The elimination of cell surface MHC class I expression blocks both insulitis and autoimmune diabetes in NOD/Lt mice. A disadvantage of this strain is that CD4⁺ T cells are not tolerant to MHC class I positive syngeneic cells. These mice provide an excellent source for insulitis-free, MHC class I-bare NOD islets for transplantation studies.

Development

The B2m^tm1Unc mutant strain was developed in the laboratory of Dr. Beverly Koller and Dr. Oliver Smithies at the University of North Carolina at Chapel Hill. It was generated by a targeted disruption of the B2m gene. The 129-derived E14TG2a ES cell line was used. The NOD/LtJ strain was produced in the laboratory of Dr. Derry Roopenian at The Jackson Laboratory by backcrossing the B2m^tm1Unc mutation 10 times to NOD/LtJ inbred mice.

Allele

Symbol: B2m^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857133
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: B2m
Marker name: beta-2 microglobulin
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin-resistance gene into the second exon.