Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand

T Takahashi, M Tanaka, CI Brannan, NA Jenkins… - Cell, 1994 - cell.com
T Takahashi, M Tanaka, CI Brannan, NA Jenkins, NG Copeland, T Suda, S Nagata
Cell, 1994cell.com
Mice homoxygous for Ipr (lymphoprolifemtion) or g/d (generalized lymphoproliferative
disease) develop lymphsdenopathy and suffer from autoimmune disease. The Ipr mice have
a mutation in a cell-surface protein, Far, that mediates apoptosis. Fas ligand (FasL) is a
tumor necrosis factor (TNF)-related type Ii membrane protein and binds to Fas. Here, mouse
Fssl gene was Isolated and locallxed to the g/d region of mouse chromosome 1. Activated
splenocytes from g/d mice express Fad mRNA. However, FasL in g/d mice carries a point …
Summary
Mice homoxygous for Ipr (lymphoprolifemtion) or g/d (generalized lymphoproliferative disease) develop lymphsdenopathy and suffer from autoimmune disease. The Ipr mice have a mutation in a cell-surface protein, Far, that mediates apoptosis. Fas ligand (FasL) is a tumor necrosis factor (TNF)-related type Ii membrane protein and binds to Fas. Here, mouse Fssl gene was Isolated and locallxed to the g/d region of mouse chromosome 1. Activated splenocytes from g/d mice express Fad mRNA. However, FasL in g/d mice carries a point mutatlon in the C-terminal region, which IshighlyconservedamongmembersoftheTNFfamily. The recombinant g/d FasL expressed in COS ceils could not induce apoptosls in ceils expressing Fss. These resuits indicate that Ipr and g/d are mutations in Fas and Fasl, respectively, and suggest important roles of the Fas system in development of T cells as well as cytotoxic T lymphocyte-mediated cytotoxicity.
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