NOD.Cg-Rag1^tm1Mom Tg(TcrbAI4)1Dvs/DvsJ

Stock number: 004348
Product name: NOD.Rag1^null.AI4bTg
Research areas: Cancer Research, Diabetes and Obesity Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These NOD.Rag1^null.AI4bTg mice express a transgene containing a rearranged Tcrb derived from the pancreatic beta cell-reactive CD8 T lymphocyte clone AI4, and are incapable of rearranging endogenous T cell receptor genes as a result of the nonfunctional Rag1^tm1Mom allele.

Detailed description

The rearranged Tcrb transgene expressed in these mice is derived from the pancreatic beta cell-reactive CD8 T lymphocyte clone AI4. The presence of the nonfunctional Rag1^tm1Mom allele renders mice incapable of rearranging endogenous T cell receptor genes. When crossed with strain NOD.Cg-Tg(TcraAI4)1Dvs-Rag1^tm1Mom/DvsJ (004347), the resulting animals that carry both the alpha and beta AI4 TCR transgenes exhibit an accelerated development of insulin-dependent diabetes mellitus (IDDM). Additionally, transgenic animals bearing both TCR transgenes offer a source of CTL precursors useful in examining the diversity of beta cell peptides recognized by the autoreactive CD8+ T lymphocytes contributing to the earliest phase of IDDM development. Homozygous mice are viable and fertile.

Development

A transgenic construct containing a Tcrb-V2/Tcrb-D/Tcrb-J cDNA segment was injected into NOD/Lt zygotes. An outcross-intercross strategy was employed to introduce an inactivated Rag1 allele from an N11 congenic stock, NOD.129S7(B6)-Rag1^tm1Mom/J mice (strain 003729).

Allele

Symbol: Tg(TcrbAI4)1Dvs
Name: transgene insertion 1, David V Serreze
MGI accession ID: MGI:3057181
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcrbAI4)1Dvs
Marker name: transgene insertion 1, David V Serreze
Chromosome: UN
Strain of origin: NOD/ShiLt
Expressed genes: Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: The rearranged Tcrb transgene expressed in these mice is derived from the pancreatic beta cell-reactive CD8 T lymphocyte clone AI4. The transgenic construct contains a Tcrb-V2/Tcrb-D/Tcrb-J cDNA segment.
General note: In conjunction with Rag1^tm1Mom

transgenic mice carrying both the alpha and beta AI4 TCR transgenes exhibit an accelerated development of insulin-dependent diabetes mellitus (IDDM).

homozygous mice are viable and fertile

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.