B6.129-Ido1^tm1Alm/J

Stock number: 005867
Product name: IDO KO
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

The lack of endogenous protein in homozygotes of these indoleamine 2,3-dioxygenase 1 knock-out mice affects immune and a number of other physiological responses. These mice may be useful in studies of pregnancy and reproductive immunology, as well as other immune response and physiological processes.

Detailed description

Homozygous mice are viable and fertile with normal immune system development and function. They exhibit no spontaneous autoimmune disorders. No gene product (mRNA or protein) from the targeted gene is detected in the epididymis. At embryonic day 10.5, endogenous protein is absent from all cells at the maternal-fetal interface when both parents are homozygous for the targeted gene. Allogeneic and syngeneic pregnancy outcomes are unaffected by this mutation. In contrast to wild-type, anti-proliferative treatments (CTLA4-Ig, IFNalpha, or CpG-ODN) do not suppress T cell expansion both in vivo and in vitro. In addition, homozygous dendritic cells isolated from lymph nodes draining (induced) tumor sites have no suppressor activity. These mice may be useful in studies of pregnancy and reproductive immunology (tryptophan degradation, T cell activation, clonal expansion) as well as autoimmune disease, tissue transplantation, fostering, acquired tolerance/T cell anergy, and immunosuppressive pathways.

Development

A targeting vector was designed to replace exons 3-5 (encode critical portions of the enzyme catalytic site) with the beta-galactosidase and neomycin resistance genes. A translational "stop" codon (TAG) that was reported to have been introduced into exon 2 is not detected in The Jackson Laboratory Repository colony. The construct was electroporated into 129/SvJ-derived embryonic stem (ES) cells and correctly targeted clones were injected into blastocysts. Male chimeric mice were mated with C57BL/6 females to produce heterozygotes. Mutant mice were backcrossed more than 10 generations to C57BL/6 before arriving at The Jackson Laboratory.

Allele

Symbol: Ido1^tm1Alm
Name: targeted mutation 1, Andrew L Mellor
MGI accession ID: MGI:3505776
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ido1
Marker name: indoleamine 2,3-dioxygenase 1
Chromosome: 8
Strain of origin: 129X1/SvJ
Molecular note: A Betagal and neomycin cassette replaced exons 3-5, which encode critical portions of the enzyme catalytic site. Also, a translation stop codon was introduced into exon 2. RT-PCR of total epididymis RNA from mutants showed no transcript was present. Western blot of mutant epididymis confirmed a lack of protein.