Mice homozygous for both the lymphoproliferation spontaneous mutation (Faslpr) and the B2mtm1Unc targeted mutation are viable and fertile. Class I molecule-deficient B2mtm1Unc mice were backcrossed to MRL/MpJ-Faslpr to study the role of MHC class I molecules in the development of systemic autoimmune disease. Double homozygous mutant mice demonstrated a substantial reduction in CD4-CD8- T cells and a diminution of autoimmune disease. Specifically, hypergammaglobulinemia; autoantibodies including anti-DNA, anti-Smith antigen, and rheumatoid factor; and glomerulonephritis were significantly reduced compared to MRL/MpJ-Faslpr homozygous mice. Moreover, the pattern of hypergammaglobulinemia suggests that the requirement for MHC class I proteins is restricted temporally to later stages of the disease.
The B2mtm1Unc mutant strain was developed in the laboratory of Dr. Beverly Koller and Dr. Oliver Smithies at the University of North Carolina at Chapel Hill. It was generated by a targeted disruption of the B2m gene. The 129-derived E14TG2a ES cell line was used. The MRL-Faslpr .129P2(B6)-B2mtm1Unc strain was produced in the laboratory of Dr. Derry Roopenian at The Jackson Laboratory by backcrossing the B2mtm1Unc mutation 10 times to MRL/MpJ-Faslpr inbred mice.
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||b2mnull; beta2M-; beta2m0; beta2mnull; beta2mo; beta2mtm1Unc; beta2MKO; beta2-m-KO; I0; MHC-I-|
|Gene Symbol and Name||B2m, beta-2 microglobulin|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Insertion of a neomycin-resistance gene into the second exon.|
|Mutations Made By|| |
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
|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.|
This double mutant strain is maintained by mating homozygous siblings. Only homozygous mice may be ordered. Expected coat color from breeding: albino
When using the MRL.Cg-B2mtm1Unc Faslpr mouse strain in a publication, please cite the originating article(s) and include JAX stock #002455 in your Materials and Methods section.