アマノ　ケンジ   Amano   天野　賢治    所属   東邦大学  医学部 医学科（大森病院）    職種   胚培養士
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice.
掲載誌名	正式名：Human molecular genetics ISSNコード：0964-6906
掲載区分	国外
巻・号・頁	11(11),pp.1251-62
著者・共著者	Subramaniam Ganesh,Antonio V Delgado-Escueta,Toshiro Sakamoto,Maria Rosa Avila,Jesus Machado-Salas,Yoshinobu Hoshii,Takumi Akagi,Hiroshi Gomi,Toshimitsu Suzuki,Kenji Amano,Kishan Lal Agarwala,Yuki Hasegawa,Dong-Sheng Bai,Tokuhiro Ishihara,Tsutomu Hashikawa,Shigeyoshi Itohara,Eain M Cornford,Hiroaki Niki,Kazuhiro Yamakawa
発行年月	2002/05/15
概要	Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause Lafora disease (LD), a progressive and invariably fatal epilepsy with periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions (Lafora bodies) in the central nervous system. To study the pathology of LD and the functions of laforin, we disrupted the Epm2a gene in mice. At two months of age, homozygous null mutants developed widespread degeneration of neurons, most of which occurred in the absence of Lafora bodies. Dying neurons characteristically exhibit swelling in the endoplasmic reticulum, Golgi networks and mitochondria in the absence of apoptotic bodies or fragmentation of DNA. As Lafora bodies become more prominent at 4-12 months, organelles and nuclei are disrupted. The Lafora bodies, present both in neuronal and non-neural tissues, are positive for ubiquitin and advanced glycation end-products only in neurons, suggesting different pathological consequence for Lafora inclusions in neuronal tissues. Neuronal degeneration and Lafora inclusion bodies predate the onset of impaired behavioral responses, ataxia, spontaneous myoclonic seizures and EEG epileptiform activity. Our results suggest that LD is a primary neurodegenerative disorder that may utilize a non-apoptotic mechanism of cell death.
PMID	12019206