NOD.Cg-Rag1^tm1Mom H2-Ab1^tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ

Stock number: 006022
Product name: NOD.DQ8, H2-Ab0^null,Rag1^null
Research areas: Cancer Research, Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These NOD mice carry human CD4 and HLA- DQ8 transgenes along with the Rag1^tm1Mom and Ab1^tm1Gru targeted mutations and are free from both autoimmune diabetes and cardiomyopathy.

Detailed description

Rag1 and H2-Ab1 deficient NOD mice carrying transgenes coding for human CD2-CD4 and HLA-DQ8 lack T and B cells, and are diabetes free. Also, unlike the H2-Ab1 deficient, transgenic CD4, HLA-DQ8 mice (see Stock No. 006021), this strain does not develop cardiomyopathy.

This model is useful in adoptive transfer experiments and to understand the role of MHC class II in autoimmunity.

Development

Congenic, H2-Ab1 deficient, NOD mice carrying transgenes coding for CD2-CD4 and DQ8(Stock No. 006021) were crossed to NOD congenic Rag1 deficient mice (Stock No. 003729) and were bred to homozygosity for the H2-Ab1^tm1Gru and Rag1^tm1Mom targeted mutations. The T1DR received NOD.Cg-Rag1^tm1Mom H2-Ab1^tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/EllJ in 2006.

Allele

Symbol: Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Name: transgene insertion 1, John F Elliott
MGI accession ID: MGI:3590082
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Marker name: transgene insertion 1, John F Elliott
Chromosome: UN
Strain of origin: NOD/MrkTac
Expressed genes: HLA-DQA1,major histocompatibility complex, class II, DQ alpha 1,human; HLA-DQB1,major histocompatibility complex, class II, DQ beta 1,human; CD4,CD4 molecule,human
Molecular note: Fertilized oocytes were co-injected with two DNA fragments: a human CD4 cDNA joined to the promoter from the human CD2 gene and a large DNA fragment, reassembled from segments of the cosmid pDCbeta2, containing the human major histocompatibility (MHC) class II alleles HLA-DQA1*0301 and HLA-DQB*0302, which together encode the dimer comprising the HLA-DQ8 molecule, plus 5' regulatory elements. Human CD4 is expressed at a low level on all T cells of transgenic mice. HLA-DQ8 is expressed in homozygous NOD mice at a level comparable to that of the endogenous NOD H2-Abeta^g7 MHC class II molecule in wild-type NOD mice.
General note: Although in NOD mice homozygous for this transgene alone endogeous NOD H2-Abeta^g7 and transgene-derived HLA-DQ8 are expressed at similar levels, virtually all CD4⁺ T-cell responses are H2Abeta1^g7 restricted (J:87013).

Allele

Symbol: Rag1^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:1857241
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Rag1
Marker name: recombination activating gene 1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Site of expression: expression is seen in bone marrow derived cell lines.
Molecular note: A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.

Allele

Symbol: H2-Ab1^tm1Gru
Name: targeted mutation 1, Michael J Grusby
MGI accession ID: MGI:2158420
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: A neomycin selection cassette was inserted into exon 2. 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.