NOD.129(B6)-Cd38^tm1Lnd Art2a^tm1Fkn Art2b^tm1Fkn/Lt

Stock number: 005347
Product name: NOD.CD38^-/-/ART^-/-
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These mice carry a triple knock-out of the Cd38, Art2a-ps, and Art2b genes and whose combined deficient T cells are resistant to NAD-induced killing in vitro. The mice also exhibit suppression of diabetes development.

Detailed description

Ubiquitously expressed CD38 and T cell-expressed ADP-ribosyltransferase 2 (ART2) are ectoenzymes competing for NAD substrate. CD38 exerts pleiotropic actions in hemopoietic and nonhemopoietic compartments via effects on calcium mobilization. ART2 is an ADP-ribosyltransferase on naive CD4+ and CD8+ T cells. The balance between T-effectors and T-regulatory cells, disturbed in CD38-deficient but ART2-intact NOD mice, is corrected in these combined CD38/ART2 deficient mice. These mice are resistant to NAD-induced killing in vitro, and diabetes development is strongly suppressed.

Development

This triple mutant was created by intercrossing NOD.129S4(B6)-Art2a^tm1Fkn Art2b^tm1Fkn/Lt and NOD.129P2(B6)-Cd38^tm1Lnd/LtJ (Stock No. 004311). F1 mice were backcrossed to NOD.129S4(B6)-Art2a^tm1Fkn Art2b^tm1Fkn/Lt to generate mice homozygous for the Art2a and Art2b alleles and heterozygous for Cd38^tm1Lnd. Subsequent matings generated the triple homozygous mutant.

Allele

Symbol: Cd38^tm1Lnd
Name: targeted mutation 1, Frances E Lund
MGI accession ID: MGI:1861803
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd38
Marker name: CD38 antigen
Chromosome: 5
Strain of origin: 129P2/OlaHsd
Molecular note: A neomycin selection cassette replaced a genomic fragment containing exons 2 and 3, which encode the putative active site of the encoded protein. Homozygous mice lacked transcripts derived from this allele (data not shown). Flow cytometry analysis on splenocytes derived from homozygous mice confirmed that no detectable protein was expressed on the cell surface.

Allele

Symbol: Art2b^tm1Fkn
Name: targeted mutation 1, Friedrich Koch-Nolte
MGI accession ID: MGI:2388827
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Art2b
Marker name: ADP-ribosyltransferase 2b
Chromosome: 7
Strain of origin: 129S4/SvJae
Molecular note: The coding region was disrupted by a hygromycin selection cassette inserted by homologous recombination. This construct was used to transfect mice in which the Art2a^tm1Fkn allele had already been created Transcript was undetected in homozygous mutant mice by RT-PCR analysis of T cells isolated from lymph nodes. FACS analysis of thymocytes and lymphocytes indicated a lack of protein expression on the cell surface.
General note: The targeting vector was electroporated into J1 ES cells carrying Art2a^tm1Fkn.

Allele

Symbol: Art2a^tm1Fkn
Name: targeted mutation 1, Friedrich Koch-Noltet
MGI accession ID: MGI:2388822
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Art2a
Marker name: ADP-ribosyltransferase 2a
Chromosome: 7
Strain of origin: 129S4/SvJae
Molecular note: The coding region was disrupted by a neomycin selection cassette inserted by homologous recombination. Transcript was undetected in homozygous mutant mice by RT-PCR analysis of T cells isolated from lymph nodes.
General note: Successfully targeted ES cells were subsequently targeted with the construct for the Art2b allele.