NOD.129(B6)-B2m^tm1Unc Ciita^tm1Ccum/BhsJ

Stock number: 005356
Product name: NOD.B2m^null, C2ta^null
Research areas: Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

These double knock-out mice exhibit absence of MHC I or MHC II cell surface expression, reduced peripheral T-cell populations, and deficiency of CD4+ and CD8+ T-cells.

Detailed description

NOD.129(B6)-B2m^tm1Unc C2ta^tm1Ccum/BhsJ is homozygous for linkage markers delineating Idd1-5, 7-10 and 13-15 loci of NOD origin and do not become diabetic. Histology indicates normal islet tissue structure with no cellular infiltration. Islets are intact and produce insulin. FACs analysis of peripheral blood cells of mice homozygote for B2m^tm1Unc and C2ta^tm1Ccum confirmed the absence of MHC I or MHC II cell surface expression, reduced peripheral T-cell populations, deficiency of CD4+ and CD8+ T-cells and there is no difference in B-cell numbers when compared with wild-type controls. Additionally, B2m^tm1Unc, C2ta^tm1Ccum double homozygous animals exhibit lower IgG titers and higher IgM titers than wild-type controls. Diabetic NOD females receiving purified islets from NOD.129(B6)-B2m^tm1Unc C2ta^tm1Ccum/BhsJ transplanted under the kidney capsule remain normal glycemic for at least 147 days post transplant as compared to diabetic NOD mice with islet transplants from either NOD.129P2(B6)-B2m^tm1Unc/J or NOD.129S2(B6)-C2ta^tm1Ccum/Flv which exhibit disease recurrence by 8 days post transplantation. Histological examination of islet grafts taken at 147 days post transplantation reveals an intact mass of insulin producing islets surrounded by cellular infiltrate. The cellular infiltrate consists mostly of CD4+ and CD8+ T-cells and macrophages. All islet grafts, independent of survival contain IFN gamma and IL10 (Young et al., 2004).

This stock is useful to help identify the mechanism by which MHC genes mediate susceptibility to T1D and the role of MHC I and II molecules in islet destruction.

Development

Using marker assisted analysis, the NOD.129(B6)-B2m^tm1Unc C2ta^tm1Ccum/Bhs strain is the result of intercrossing NOD.129P2(B6)-B2m^tm1Unc/J to NOD.129S2(B6)-C2ta^tm1Ccum/Flv prior to making homozygote for both the C2ta^tm1Ccum and B2m^tm1Unc alleles. FACS analysis of peripheral blood was used as an indicator that both the C2ta^tm1Ccum and B2m^tm1Unc are homozygote (Young et al., 2004). In 2005, The Jackson Laboratory received NOD.129(B6)-B2m^tm1Unc C2ta^tm1Ccum/BhsJ at generation N9F7.

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.

Allele

Symbol: Ciita^tm1Ccum
Name: targeted mutation 1, Cheong-Hee Chang
MGI accession ID: MGI:1857456
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ciita
Marker name: class II transactivator
Chromosome: 16
Strain of origin: 129S2/SvPas
Molecular note: A genomic fragment containing exons which encode critical regions of the protein was replaced with a neomycin selection gene. Northern blot analysis on RNA derived from homozygous mice demonstrated that no detectable protein was produced from this allele.