NODCaj.129S2(B6)-H2-Ab1^tm1Doi/LwnJ

Stock number: 010966
Product name: NOD.Ab⁰
Strain synonyms: NOD.Ab0, NOD.Ab null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

NOD. H2-Ab1 deficient mice are diabetes resistant and exhibit a dramatic decrease of CD4⁺ T cells when compared to NOD/ShiLtJ. This model may be useful to facilitate the engraftment of immune cells in adoptive transfer experiments and to understand the role of MHC class II in autoimmunity.

Detailed description

Mice homozygous for MHC class II gene, H2-Ab1 targeted mutation, commonly referred to as NOD-Ab⁰, are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. NOD. Ab⁰ mice are diabetes resistant. MHC class II gene products (mRNA or protein) are not detected. FACS analysis of peripheral blood lymphocytes (PBL's) indicates a dramatic decrease is observed in the number of CD4⁺ T cells when compared to NOD/ShiLtJ (Stock No. 001976). In addition, FACS of PBL's verifies the MHC class I variant K^b (129S2 derived) is in linkage to the Ab⁰ mutation. SNP and Mit marker assisted analysis indicates the Chromosome 17 markers D17Mit27 through D17Mit176 to be of 129S2 origin and is about 29 mb long. No other non-NOD contaminating regions were identified. In 2008, the T1DR received this stock at N11F?. This strain was mated to NOD/LtJ (Stock No. 001976) once prior to breeding to homozygosity. This model may be useful to facilitate the engraftment of immune cells in adoptive transfer experiments and to understand the role of MHC class II in autoimmunity.

Development

A construct containing a neomycin expression cassette was inserted into the second exon of H2-Ab1 gene. The construct was transfected into D3, 129S2/SvPas, embryonic stem (ES) cells, which carries a deletion in the promoter region of the H2-Ea. These ES cells were injected into C57BL/6 blastocysts. Progeny of chimeric mice were mated with C57BL/6. The H2-Ab1^tm1Doi mutation was backcrossed for 10 generations to NOD/CaJ prior to making homozygous. In 2009, SNP and Mit marker testing performed by the T1DR indicate that there is no contaminating genome outside of the congenic region on Chr. 17.

Allele

Symbol: H2-Ab1^tm1Doi
Name: targeted mutation 1, Christophe Benoist and Diane Mathis
MGI accession ID: MGI:1927483
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: H2-Ab1
Marker name: histocompatibility 2, class II antigen A, beta 1
Chromosome: 17
Strain of origin: 129S2/SvPas
Molecular note: The second exon was disrupted by the insertion of a neomycin resistance gene. In addition, the ES cell line used was derived from the 129S2/SvPas strain, which carries a deletion in the promoter region of H2-Ea. Consequently, these MHC class II molecule-deficient mice lacked cell surface expression of both class II-A and class II-E MHC proteins.