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Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet‐activating factor receptor
Author(s) -
Ishii Satoshi,
Nagase Takahide,
Tashiro Fumi,
Ikuta Koichi,
Sato Sayuri,
Waga Iwao,
Kume Kazuhiko,
Miyazaki Junichi,
Shimizu Takao
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.1.133
Subject(s) - biology , genetically modified mouse , platelet activating factor , transgene , in vivo , immunology , pathophysiology , carcinogenesis , receptor , cancer research , methacholine , microbiology and biotechnology , endocrinology , medicine , lung , respiratory disease , cancer , genetics , gene , biochemistry
Although platelet‐activating factor (PAF) has been shown to exert pleiotropic effects on isolated cells or tissues, controversy still exists as to whether it plays significant pathophysiological roles in vivo . To answer this question, we established transgenic mice overexpressing a guinea‐pig PAF receptor (PAFR). The transgenic mice showed a bronchial hyperreactivity to methacholine and an increased mortality when exposed to bacterial endotoxin. An aberrant melanogenesis and proliferative abnormalities in the skin were also observed in the transgenic mice, some of which spontaneously bore melanocytic tumors in the dermis after aging. Thus, PAFR transgenic mice proved to be a useful model for studying the basic pathophysiology of bronchial asthma and endotoxin‐induced death, and screening of therapeutics for these disorders. Furthermore, our findings provide new insights regarding the role of PAF in the morphogenesis of dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo .