NOD.Cg-Prkdc^scid H2-Ab1^tm1Doi Tg(HLA-DQA1,HLA-DQB1)1Dv/SzJ

Stock number: 004606
Product name: NOD.scid AB0^nullDQ8
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Detailed description

This strain which is MHC II deficient and has no functional T or B cells expresses a humanized transgenic HLA-DQ8 molecule that has been linked to IDDM development. This model is a valuable genetic tool for identifying the role of HLA-DQ8 in Type 1 Diabetes.

Development

A 30kb DNA fragment containing the DQA*0301 gene from cosmid H11A and a 38kb DNA fragment containing the DQB*0302 gene from cosmid X10A were microinjected into (CBA/J x B10.M)F2 embryos. To establish germline transmission founders were mated to the B10.M strain. This transgene was then mated to (B6x129)-H2-Ab1 targeted mutation. The transgene positive, H2-Ab1 mice were intercrossed to make homozygote for the H2-Ab1 targeted allele (Nabozny et al, 1996). Flynn et al, 2002, backcrossed the transgenic HLA-DQ8, H2-Ab1 mice to NOD for 10 generations. Schultz et al (Unpublished), backcrossed the NOD-Tg(HLA-DQ8)1Sz H2-Ab1^tm1Doi to NOD.Cg-Prkdc^scid H2-Ab1^tm1Doi/Sz. In 2003, the Type 1 Diabetes Resource received NOD.Cg-Prkdc^scidTg(HLA-DQ8)1Sz H2-Ab1^tm1Doi/Sz at [NE10F?+4p]+F1.

Allele

Symbol: Tg(HLA-DQA1,HLA-DQB1)1Dv
Name: transgene insertion 1, Chella David
MGI accession ID: MGI:3586633
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(HLA-DQA1,HLA-DQB1)1Dv
Marker name: transgene insertion 1, Chella David
Chromosome: UN
Strain of origin: (CBA/J x B10.M-H2^f)F2
Expressed genes: HLA-DQA1,major histocompatibility complex, class II, DQ alpha 1,human; HLA-DQB1,major histocompatibility complex, class II, DQ beta 1,human
Molecular note: A 30-kb human genomic DNA fragment containing the entire HLA-DQA1*0301 gene and a promoter-truncated HLA-DQB1*0302 gene from cosmid H11A and a 38-kb DNA fragment containing the entire HLA-DQB1*0302 gene from cosmid X10A were coinjected.
General note: Flow cytometric analysis of peripheral blood leukocytes (PBL) using a monoclonal antibody to HLA-DQ demonstrated that transgenic mice express the transgenes. 25-40% of the PBLs of mixed-background transgenic mice homozygous for the targeted MHC class II mutation H2-Ab1^tm1Dim express the transgenes. Lymph nodes of such mice contain three-fold the levels of CD4⁺ CD44⁺ T-cells as do those of nontransgenic MHC class II-deficient mice, levels similar to those of class II-sufficient mice. Immunization of transgenic H2-Ab1^tm1Dim homozygous mice with bovine collagen II results in a strong IgG antibody response to the immunogen, and 66% of these mice develop severe, persistent arthritis. (J:88296)

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.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
Molecular note: A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*).