Hemizygous males carrying the recessive, spontaneous scurfy mutation exhibit massive lymphoproliferation and inflammatory infiltration in several organs, and die by three weeks of age.
Christophe Benoist, Joslin Diabetes Center
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.
Foxp3, forkhead box P3, located on the X-Chr. (2.1cM) is necessary for Treg development. An X-linked, spontaneous mutation, Foxp3sf (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 Tyrch/p Tyrc 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 Foxp3sf/+ females to C57BL/6NTac males. B6.Cg-Foxp3sf 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 Synonym(s)||Scurfy; sf|
|Gene Symbol and Name||Foxp3, forkhead box P3|
|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.|
Only the heterozygous female will be available for distribution, the hemizygous male dies too early to be shipped. Breeder pair is het female x wildtype or NOD/ShiLtJ (Stock No. 001976) male (not reciprocal). Affected mutant is hemizygous male. Homozygous female would also be affected, but traditional breeding schemes will not allow for the female to be born.
When using the NOD.Fox-p3 mouse strain in a publication, please cite the originating article(s) and include JAX stock #006775 in your Materials and Methods section.