NOD.MRL-Fas^lpr/Dvs

Stock number: 004922
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs

Development

The Fas^lpr mutation was backcrossed from MRL/MpJ-Fas^lpr/J onto NOD/LtDvs for 13 backcross generations in the laboratory of Dr. David Serreze. The strain was then intercrossed and made homozygous for Fas^lpr. It was cryopreserved in 2006 at generation N13F8.

Allele

Symbol: Fas^lpr
Name: lymphoproliferation
MGI accession ID: MGI:1856334
Generation method: Spontaneous
Attributes: Hypomorph
Synonyms: Fas-; Fas-def; lpr; MRL/lpr; Tnfrf6^lpr; Tnfrsf6^lpr; Tnfrsf6lpr
Marker symbol: Fas
Marker name: Fas (TNF receptor superfamily member 6)
Marker synonyms: ALPS1A; APO-1; APT1; CD95; FAS1; FASTM; TNFR6; TNFRSF6
Chromosome: 19
Strain of origin: MRL/Mp
Molecular note: Southern blotting experiments indicated that the mutation is a genomic rearrangement within the gene, probably within the second intron. Sequencing of genomic DNA and RT-PCR products from homozygous mutant mice revealed the insertion of an early transposable element (ETn) into intron 2. RT-PCR analysis of liver and thymus mRNA showed that the presence of the ETn leads to premature termination of transcription at the long terminal repeat (LTR) of the ETn and aberrant mRNA splicing. The mutation is "leaky," however, as full-length mRNA and a longer splice product incorporating a segment of the ETn as an extra intron are detected in the thymus at low levels.
General note: Fas^lpr, lymphoproliferation, recessive. This mutation was found during inbreeding of a strain MRL/Mp derived from crosses among strains LG, AKR, C3H, and C57BL/6. The resemblance has led to extensive use of Fas^lpr mice in attempts to determine the etiology of SLE and to evaluate therapies. However, the human APT1 gene (OMIM 134637) encodes the FAS antigen; Tnfrsf6 is not the homolog of the human (SLE) gene. The Cd72^c haplotype is a modifier of Fas^lpr-induced autoimmune disease. J:204782