Mice homozygous for the lymphoproliferation spontaneous mutation (Faslpr) show systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, arthritis, and immune complex glomerulonephrosis. This mouse is a model for systemic lupus erythematosus-like autoimmune syndromes.Read More +
This strain is homozygous for the retinal degeneration allele Pde6brd1.
Mice homozygous for the lymphoproliferation spontaneous mutation (Faslpr) show systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, arthritis, and immune complex glomerulonephrosis. Onset and severity of symptoms associated with the Faslpr allele is strain-dependent. For example, lymphoproliferation varies greatly with congenic strain C57BL/6J-Faslpr/Faslpr at a 24 fold increase over control lymph node weight, MRL/Mp-Faslpr/Faslpr at 75 fold and congenic strain C3H/HeJ-Faslpr/Faslpr highest at 116 fold increase over control lymph node weight (Morse et al 1985). Variance in renal pathology ranks from extensive in MRL/Mp-Faslpr/Faslpr at 4 to 7 months to negligible at 14 to 16 months in mice with C57BL/6J and C3H/HeJ backgrounds and homozygous for Faslpr (Kelley and Roths 1985). Spontaneous production of anti-dsDNA autoantibodies is likewise affected with percentage binding of radiolabeled dsDNA in Faslpr/Faslpr mice varying from 5 percent on C57BL/6J to 26 percent on C3H/HeJ to as high as 49 percent on MRL/Mp (Izui et al 1984). Female MRL/Mp-Faslpr mice die at an average age of 17 weeks of age and males at 22 weeks. This compares to between 42 and 52 weeks in females on the C57BL/6J or C3H/HeJ background (Roths 1987). This mouse is a model for systemic lupus erythematosus-like autoimmune syndromes.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
The first observation of the massive lymphoproliferation occurred in the 12th generation of inbreeding of strain MRL/Mp derived from crosses among strains LG, AKR, C3H, and C57BL/6 at The Jackson Laboratory. At the 13th generation it was possible to select both lymphoproliferative positive and negative sublines which had an estimated 89% of their genomes in common. The mutant gene, Faslpr, was transferred to the MRL negative strain by 5 cycles of cross-intercross matings thus reducing the estimate of residual heterozygosity to 1% from 11%. The Faslpr gene was transferred to C3H/HeJ in the late 1970's (Murphy and Roths. Mouse News Letter 1978,58:51).
|Allele Type||Spontaneous (Hypomorph)|
|Allele Synonym(s)||Fas-; Fas-def; lpr; MRL/lpr; Tnfrf6lpr; Tnfrsf6lpr; Tnfrsf6lpr|
|Gene Symbol and Name||Fas, Fas (TNF receptor superfamily member 6)|
|Strain of Origin||MRL/Mp|
|General Note||Faslpr, 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 Faslpr 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 Cd72c haplotype is a modifier of Faslpr-induced autoimmune disease. J:204782|
|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.|
When using the C3-lymphoproliferation mouse strain in a publication, please cite the originating article(s) and include JAX stock #000480 in your Materials and Methods section.