CBA/KlJms-Fas^lpr-cg/J

Stock number: 001876
Product name: lymphoproliferation complementing gld
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs

Description

These mice carry a spontaneous mutation at the Fas locus characterized by massive lymphadenopathy.

Detailed description

Mice homozygous for the lymphoproliferation complementing gld spontaneous mutation (Fas^lpr-cg) are viable and fertile. Homozygous mutant mice are characterized by massive lymphadenopathy. Fas^lpr-cg complemented both Fas^lpr and the Fasl^gld mutation in that double heterozygotes with either mutation had lymphadenopathy. However, further crosses showed the new mutation to be an allele at Fas^lpr. Like Fas^lpr and Fasl^gld homozygotes, CBA/KlJms-Fas^lpr-cg homozygotes produce antibodies to some nuclear antigens, such as dsDNA, ssDNA, and poly(ADP-ribose); however, they do not produce anti-erythrocyte antibodies. Although they exhibit lymphoid cell infiltration around blood vessels in lung, liver, and kidney, they lack the immune-complex glomerulonephritis, vasculitis, and interstitial pneumonia characteristic of Fas^lpr homozygotes.

Development

The Fas^lpr-cg mutation occurred spontaneously in a subline of the inbred strain CBA/KlJms maintained at the Institute of Medical Science in Tokyo. Fas^lpr-cg complemented both the Fas^lpr and the Fasl^gld mutations in that double heterozygotes with either mutation had lymphadenopathy.

Allele

Symbol: Fas^lpr-cg
Name: lymphoproliferation complementing gld
MGI accession ID: MGI:1856335
Generation method: Spontaneous
Marker symbol: Fas
Marker name: Fas (TNF receptor superfamily member 6)
Chromosome: 19
Strain of origin: CBA/KlJms
Molecular note: A T-to-A transversion point mutation at coding nucleotide 737 results in replacement of a highly conserved isoleucine by asparagine at position 246 (p.I246N) in the cytoplasmic region of the encoded protein.
General note: This mutation, which produces massive lymphadenopathy in homozygotes, occurred spontaneously in a subline of the inbred strain CBA/KlJms maintained at the Institute of Medical Science in Tokyo. Fas^lpr-cg complemented both Fas^lpr and the generalized lymphoproliferative disease Fasl^gld mutation in that double heterozygotes with either mutation had lymphadenopathy. However, further crosses showed the new mutation to be an allele at Fas^lpr (J:24805). Like Fas^lpr and Fasl^gld mutant homozygotes, CBA-Fas^lpr-cg/Fas^lpr-cg mutants produce antibodies to some nuclear antigens, such as dsDNA, ssDNA, and poly(ADP-ribose); however, they do not produce anti-erythrocyte antibodies. Although they exhibit lymphoid cell infiltration around blood vessels in lung, liver, and kidney, they lack the immune-complex glomerulonephritis, vasculitis, and interstitial pneumonia characteristic of Fas^lpr homozygotes (J:616). Fas^lpr-cg homozygotes on the MRL genetic background developed glomerulonephritic lesions similar to those of MRL/MpJ-Fas^lpr mutants, although at a lower frequency, suggesting MRL/MpJ background genes control this aspect of the disease (J:1753). Studies of Fas^lpr and Fas^lpr-cg homozygotes in athymic nude (Hfh11^nu/Hfh11^nu) mice show that the thymus is critical for lymphadenopathy and autoimmunity (J:582).