NOD.Cg-Stat4^tm1Gru Thy1^a Ifngr1^tm1Agt Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/LmbrJ

Stock number: 024476
Product name: (NOD.STAT4 KO x NOD BDC Thy1.1) x (NOD.IFNgR KO)
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These mutant mice carry Stat4 and Ifngr1 knock out alleles, the Tg(TcraBDC2.5,TcrbBDC2.5)1Doi and Thy1^a, and are defective in generation of Th1 cells. This strain has applications in studies of Type 1 diabetes and for adoptive transfer studies.

Detailed description

These mice are homozygous for the Stat4^tm1Gru, Thy1^a Ifngr1^tm1Agt targeted mutation alleles, homozygous for the Thy1^a spontaneous mutation allele and hemizygous for the Tg(TcraBDC2.5,TcrbBDC2.5)1Doi transgene. Unable to respond to IL12 and IFNgamma, the mutant mice are defective in generation of Th1 cells.

Development

Homozygote NOD.129S2-Stat4^tm1Gru/JbsJ (Stock No. 004671) mice, homozygote NOD.NON-Thy1^a/1LtJ (Stock No. 004483) mice, mice on the NOD background homozygous for the Ifngr1^tm1Agt allele and mice on the NOD background hemizygous for the Tg(TcraBDC2.5,TcrbBDC2.5)1Doi transgene were bred together to generate this mutant strain.

Allele

Symbol: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi
Name: transgene insertion 1, Christophe Benoist
MGI accession ID: MGI:2181203
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi
Marker name: transgene insertion 1, Christophe Benoist
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F2
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: This transgene results from the coinjection of two constructs derived from diabetogenic T-cell clone BDC2.5. The Tcra construct contains a rearranged Tcra sequence (V alpha J alpha) that begins 20 bp 5' of the ATG site and ends 30 bp 3' of the splice donor sequence of J alpha 17. The 6.5 Tcrb construct contains rearranged Tcrb sequence (V beta D beta J beta) flanked by 2 kb of 5' regulatory sequences and 3.5 kb of 3' DNA containing the unrearranged J beta 1.3 to J beta 1.6 sequences, and precedes a 12 kb sequence containing the C beta 2 region.

Allele

Symbol: Stat4^tm1Gru
Name: targeted mutation 1, Michael J Grusby
MGI accession ID: MGI:1857248
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Stat4
Marker name: signal transducer and activator of transcription 4
Chromosome: 1
Strain of origin: 129S2/SvPas
Molecular note: The exon encoding amino acids 263 through 314 was disrupted by the insertion of a neomycin selection cassette. The encoded protein was undetectable in the thymi and lymph nodes of homozygous mutant mice by immunoblot analysis.

Allele

Symbol: Ifngr1^tm1Agt
Name: targeted mutation 1, Michel Aguet
MGI accession ID: MGI:1857286
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ifngr1
Marker name: interferon gamma receptor 1
Chromosome: 10
Strain of origin: 129S7/SvEvBrd-Hprt⁺
Molecular note: Insertion of a neomycin cassette into exon V, which encodes an extracellular membrane-proximal portion of the receptor.

Allele

Symbol: Thy1^a
Name: a variant
MGI accession ID: MGI:3579311
Generation method: Not Applicable
Marker symbol: Thy1
Marker name: thymus cell antigen 1, theta
Chromosome: 9
Strain of origin: Not Applicable
Site of expression: The Thy1 locus determines a surface antigen present on cells of the thymus, a number of mouse leukemias, brain, and in lesser amounts on lymph node and spleen cells.
Molecular note: The allele Thy1^a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains.
General note:

The Thy1 locus determines a surface antigen present on cells of the thymus, a number of mouse leukemias, brain, and in lesser amounts on lymph node and spleen cells. The allele Thy1^a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains; the allele Thy1^b determines an antigenic specificity, Thy-1.2, found in the C3HeB/Fe and many other strains (J:5243, J:5012, J:4469). The Thy1 antigen is probably present on all T lymphocytes and absent from all B lymphocytes, and it thus serves as a valuable T-cell marker (J:5243). It is very widely used in experiments designed to determine the distribution and function of T-cells. Thy1 specifies a T-cell surface glycoprotein, T25, with a molecular weight of 25 kDa (J:5707). The protein appears to be anchored in the cell membrane by a lipid that is either phosphotidylinositol or closely related to it (J:12016). Thy1 may function in the cell membrane as a signal transduction molecule (J:8333). The Thy1 locus, or possibly a gene closely linked to it, controls quantitative expression of a protein that is the same size as Thy1 and is expressed on thymus and brain but not on lymph node and spleen cells (J:7900).