NOD.Cg-Rag1^tm1Mom H2-Ab1^tm1Gru Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell/EllJ

Stock number: 006024
Product name: NOD.DQ6, 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-DQ6 transgenes resulting in a lack of T and B cells.

Detailed description

Rag1 and H2-Ab1 deficient NOD mice carrying transgenes encoding humanized CD4 and HLA-DQ6 lack T and B cells and are free of autoimmune diabetes and cardiomyopathy, and do not develop thyroiditis.

This model is useful in adoptive transfer experiments and in studying MHC class II-based resistance and susceptibility in autoimmunity.

Development

Congenic, H2-Ab1 deficient, NOD mice carrying transgenes encoding CD4 and a human genomic fragment containing the entire HLA-DQ6 gene (DQA1*0102, DQB1*0602, Stock No. 006023) were crossed to congenic Rag1 deficient NOD mice (Stock No. 003729), and were bred to homozygosity for the H2-Ab1^tm1Gru and Rag1^tm1Mom targeted mutations. The T1DR received this strain in 2006.

Allele

Symbol: Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell
Name: transgene insertion N8, John F Elliott
MGI accession ID: MGI:3590083
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell
Marker name: transgene insertion N8, John F Elliott
Chromosome: UN
Strain of origin: NOD/ShiLtJ
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: The human CD4 gene lacking one exon but including its promoter was fused downstream of a mouse CD4 enhancer element then mixed with a large DNA fragment containing both HLA-DQA*0102 and HLA-DQB*0602 and injected into NOD/LtJ one celled embryos. A single founder line is maintained.

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-Hprt⁺
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.