NOD.129P2(B6)-B2m^tm1Unc Tg(HLA-A24/H2-D/B2M)3Dvs/J

Stock number: 010565
Product name: NOD-H24/HHD
Strain synonyms: NOD.A24/HHD
Research areas: Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

This model is useful for identifying potential HLA-A24 restricted diabetogenic T cell responses in humans and may also serve as a useful control for the HLA-A2.1 transgenic model (Stock No. 006611 - NOD.129P2(B6)-B2m^tm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ)

Detailed description

NOD mice carrying only the HLA-A24/H2-D/B2M transgene and homozygous for the B2m^tm1Unc mutation, commonly referred to as NOD.B2mnull. A24/HHD, are viable, normal in size, do not display any gross physical or behavioral abnormalities and are reported to be poor breeders. The presence of the transgene in the B2m deficient background restores CD8+ T cells, but at a significantly lower level than in NOD inbred mice. Due to the covalently linked nature of the B2m component incorporated into the transgene, the transgenic construct is unable to rescue expression of murine MHC class I molecules in the NOD. B2m deficient (Stock No. 003914) mice. FACS analysis confirms the NOD. B2m null. A24/HHD mice express human HLA-24, but no murine MHC class I molecules. NOD.B2m null, A24/HHD mice develop insulitis, but progression to overt diabetes is reported to be rare. This model provides humanized HLA-24 restricted T cells that will be useful tools to identify MHC class I epitopes recognized by CD8+ T cells in type 1 diabetes patients, and may serve as control for Stock 6611- NOD.129P2(B6)-B2m^tm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ.

Development

Both HLA-A2.1 and HLA-24 have been proposed as MHC class I molecules associated with Type 1 Diabetes in humans. This transgene encodes human B2-microglubulin (B2M) covalently linked to the alpha1 and alpha2 peptide binding domains of the human HLA-24 MHC class I gene, as well as the alpha3, cytoplasmic and transmembrane domains of the murine H2-D^b class I variant. The transgene was injected into NOD/ShiLtDvs embryos. Progeny of founder #3 were crossed to Stock No. 003914 - NOD.129P2(B6)-B2m^tm1Unc/Dvs homozygous mice prior to intercrossing. In 2009, the T1DR received this strain at generation N2F6.

Allele

Symbol: Tg(HLA-A24/H2-D/B2M)3Dvs
Name: transgene insertion 3, David Serreze
MGI accession ID: MGI:3848818
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: A24/HHD
Marker symbol: Tg(HLA-A24/H2-D/B2M)3Dvs
Marker name: transgene insertion 3, David Serreze
Marker synonyms: A24/HHD
Chromosome: UN
Strain of origin: NOD/ShiLtDvs
Expressed genes: B2M,beta-2-microglobulin,human; H2-D,histocompatibility 2, D region,mouse, laboratory; HLA-A,major histocompatibility complex, class I, A,human
Site of expression: Widespread on nucleated cells.
Molecular note: This transgene encodes human B2-microglubulin (B2M) covalently linked to the alpha1 and alpha2 peptide binding domains of the human HLA-A24 MHC class I gene, as well as the alpha3, cytoplasmic and transmembrane domains of the murine H2-Db class I variant. Human HLA-A2.1 and HLA-A24 have both been associated with T1D in humans.

Allele

Symbol: B2m^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857133
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: b2m^null; beta2M-; beta2m⁰; beta2m^null; beta2m^o; beta2m^tm1Unc; beta2MKO; beta2-m-KO; I⁰; MHC-I^-
Marker symbol: B2m
Marker name: beta-2 microglobulin
Marker synonyms: beta 2 microglobulin; beta2-m; IMD43; Ly-m11
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin-resistance gene into the second exon.