NOD.Cg-Foxp3^sf/DoiJ

Stock number: 006775
Product name: NOD.Fox-p3
Strain synonyms: NOD-scurfy
Research areas: Cell Biology Research, Dermatology Research, Developmental Biology Research, Diabetes and Obesity Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Reproductive Biology Research, Research Tools

Description

Hemizygous males carrying the recessive, spontaneous scurfy mutation exhibit massive lymphoproliferation and inflammatory infiltration in several organs, and die by three weeks of age.

Detailed description

Scurfy mice develop an X-linked lymphoproliferative disease resulting from defective T cell tolerance. By 3 weeks of age, Foxp3-deficient NOD mice suffer massive lymphoproliferation and inflammatory infiltration in lungs, liver, skin, pancreas, kidneys, stomach, colon, fat and muscles and die by three weeks of age. At 14 days of age, NOD.Foxp3-deficient mice developed exocrine pancreatitis and occasional peri-insulitis; however invasive insulitis and diabetes were not observed.

In a NOD.Foxp3-deficient, BDC2.5 TCR transgenic model, mice experienced markedly decreased lymphoproliferation, yet 100% were diabetic by 20 days of age.

This congenic NOD scurfy model is useful to study the role of Foxp3-dependent regulatory T cells on diabetes development.

Development

Foxp3, forkhead box P3, located on the X-Chr. (2.1cM) is necessary for Treg development. An X-linked, spontaneous mutation, Foxp3^sf (scurfy) results in loss of function of the Foxp3 gene which leads to a genetic deficit of regulatory T cells. The scurfy mutation arose spontaneously at the Oak Ridge National Laboratory in 1949 in the partially inbred MR stock. This strain was a multiple recessive stock of seven mutations, primarily coat color mutations. Scurfy was maintained either by backcross onto 129/Rl-p Tyr^ch/p Tyr^c or by breeding heterozygous females to (C3H/Rl x 101/Rl)F1 or (101/Rl x C3H/Rl)F1 males at each generation to keep it on a non-inbred background. Means et al. obtained scurfy mice from Yvonne Boyd at Harwell where they were maintained by breeding to (C3H/Rl x 101/Rl)F1. Means et al. backcrossed Foxp3^sf/+ females to C57BL/6NTac males. B6.Cg-Foxp3^sf mice were backcrossed to NOD. In 2007, the T1DR received this strain at N15 and mated to NOD/ShiLtJ (Stock No. 001976) for 1 generation prior to sibling mating.

Allele

Symbol: Foxp3^sf
Name: scurfy
MGI accession ID: MGI:1857034
Generation method: Spontaneous
Synonyms: Scurfy; sf
Marker symbol: Foxp3
Marker name: forkhead box P3
Marker synonyms: AIID; DIETER; IPEX; JM2; PIDX; RGD1562112; scurfin; XPID
Chromosome: X
Strain of origin: STOCK MR
Molecular note: Insertion of two adenosine residues into exon 8, resulting in a 2 bp shift in the reading frame. This allele is predicted to produce a truncated protein lacking the carboxy-terminal forkhead domain.