NOD.Cg-Prkdc^scid Emv30^b Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ

Stock number: 006605
Product name: NOD.scid HHD
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

These transgenic mice express a chimeric transgene containing  the alpha1 and alpha2 binding domains of the human histocompatibility complex (MHC) class I HLA-A2.1 allele covalently linked to the human B2m and the alpha3, cytoplasmic and transmembrane domains of the murine H2-D^b on the Type 1 diabetes-susceptible immunodeficient NOD/ShiLtDvs-Prkdc^scid background.

Detailed description

Although NOD mice that carry this transgene (Stock No. 006604) develop diabetes significantly earlier than do NOD/ShiLtDvs (NOD) controls, this transgenic strain harbors the Prkdc^scid mutation (characterized by an absence of functional T cells and B cells), and therefore does not become diabetic. This strain is useful for adoptive transfer experiments, and as a source of insulitis free pancreatic islets. Mice do not carry the endogenous ecotropic murine leukemia virus (variant b indicates absence of the provirus).

Development

This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene and the alpha3, cytoplasmic and transmembrane domains of the murine H2-D^b protein. The transgene was injected into NOD/ShiLtDvs embryos. Transgenic offspring were mated to NOD.Prkdc^scid Emv30^b (Stock No. 002313), prior to sibling mating and fixing for homozygosity. In 2007, the T1DR received this stock at generation N2F2.

Allele

Symbol: Tg(HLA-A/H2-D/B2M)1Dvs
Name: transgene insertion 1, David Serreze
MGI accession ID: MGI:3711057
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: HDD; HHD
Marker symbol: Tg(HLA-A/H2-D/B2M)1Dvs
Marker name: transgene insertion 1, David Serreze
Marker synonyms: HDD; HHD
Chromosome: UN
Strain of origin: NOD/ShiLtDvs
Expressed genes: B2M,beta-2-microglobulin,human; HLA-A,major histocompatibility complex, class I, A,human
Molecular note: This transgene encodes a human B2-microglubulin (B2M) covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene, and the alpha3, cytoplasmic and transmembrane domains of the murine H2-D^b. The construct was injected into fertilized NOD/ShiLtDvs oocytes. The construct was originally described in J:41077 and used to create a different transgenic line.
General note: The HDD construct was created and used to generate a differnet transgenic mouse line in J:41077.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Synonyms: scid
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Marker synonyms: DNAPDcs; DNAPK; DNA-PK; DNAPKc; DNA-PKC; DNA-PKcs; DNPK1; DOXNPH; dxnph; HYRC; HYRC1; IMD26; p350; S473K; slip; XRCC7
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*).

Allele

Symbol: Emv30^b
Name: endogenous ecotropic murine leukemia virus, absent
MGI accession ID: MGI:1857806
Generation method: Not Applicable
Synonyms: null
Marker symbol: Emv30
Marker name: endogenous ecotropic MuLV 30
Marker synonyms: Emv-30
Chromosome: 11
Strain of origin: Not Applicable
General note: The provirus is missing from C57BLKS/J and from the NOR/LtDn stock which was derived from an NOD subline genetically contaminated with C57BLKS/J (J:14300, J:29951).