TY - JOUR
T1 - Generalized lymphoproliferative disease in mice, caused by a point mutation in the fas ligand
AU - Takahashi, Tomohiro
AU - Tanaka, Masato
AU - Brannan, Camllynn I.
AU - Jenkins, Nancy A.
AU - Copeland, Neal G.
AU - Suda, Takashi
AU - Nagata, Shigekazu
N1 - Funding Information:
We are grateful to Dr. P. Golstein for valuable discussions. We thank Dr. A. Matsuzawa for g/d mice, D. J. Gilbert for excellent technical assistance, and Ms. K. Mimura for secretarial assistance. This work was supported in part by grants in aid from the Ministry of Education, Science, and Culture of Japan, and by the National Cancer Institute, Department of Health and Human Services, under contract NOI-CO-74101 with Advanced Bioscience Laboratories.
PY - 1994/3/25
Y1 - 1994/3/25
N2 - Mice homozygous for lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) develop lymphadenopathy and suffer from autoimmune disease. The lpr mice have a mutation in a cell-surface protein, Fas, that mediates apoptosis. Fas ligand (FasL) is a tumor necrosis factor (TNF)-related type II membrane protein and binds to Fas. Here, mouse Fasl gene was isolated and localized to the gld region of mouse chromosome 1. Activated splenocytes from gld mice express Fasl mRNA. However, FasL in gld mice carries a point mutation in the C-terminal region, which is highly conserved among members of the TNF family. The recombinant gld FasL expressed in COS cells could not induce apoptosis in cells expressing Fas. These results indicate that lpr and gld 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.
AB - Mice homozygous for lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) develop lymphadenopathy and suffer from autoimmune disease. The lpr mice have a mutation in a cell-surface protein, Fas, that mediates apoptosis. Fas ligand (FasL) is a tumor necrosis factor (TNF)-related type II membrane protein and binds to Fas. Here, mouse Fasl gene was isolated and localized to the gld region of mouse chromosome 1. Activated splenocytes from gld mice express Fasl mRNA. However, FasL in gld mice carries a point mutation in the C-terminal region, which is highly conserved among members of the TNF family. The recombinant gld FasL expressed in COS cells could not induce apoptosis in cells expressing Fas. These results indicate that lpr and gld 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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U2 - 10.1016/0092-8674(94)90375-1
DO - 10.1016/0092-8674(94)90375-1
M3 - Article
C2 - 7511063
AN - SCOPUS:0028223847
VL - 76
SP - 969
EP - 976
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -