ナカノ　ヒロヤス   Nakano Hiroyasu   中野　裕康    所属   東邦大学  医学部 医学科    東邦大学  医学部 医学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome
掲載誌名	正式名：Sci Rep ISSNコード：2045-2322
掲載区分	国外
出版社	Springer
巻・号・頁	6,pp.37200
著者・共著者	Sakata K, Araki K, Nakano H, Nishina T, Komazawa-Sakon S, Murai S, Lee GE, Hashimoto D, Suzuki C, Uchiyama Y, Notohara K, Gukovskaya AS, Gukovsky I, Yamamura KI, Baba H, Ohmuraya M.
発行年月	2016/11
概要	The loss-of-function mutations of serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with human chronic pancreatitis, but the underlying mechanisms remain unknown. We previously reported that mice lacking Spink3, the murine homologue of human SPINK1, die perinatally due to massive pancreatic acinar cell death, precluding investigation of the effects of SPINK1 deficiency. To circumvent perinatal lethality, we have developed a novel method to integrate human SPINK1 gene on the X chromosome using Cre-loxP technology and thus generated transgenic mice termed "X-SPINK1". Consistent with the fact that one of the two X chromosomes is randomly inactivated, X-SPINK1 mice exhibit mosaic pattern of SPINK1 expression. Crossing of X-SPINK1 mice with Spink3+/- mice rescued perinatal lethality, but the resulting Spink3-/-;XXSPINK1 mice developed spontaneous pancreatitis characterized by chronic inflammation and fibrosis. The results show that mice lacking a gene essential for cell survival can be rescued by expressing this gene on the X chromosome. The Spink3-/-;XXSPINK1 mice, in which this method has been applied to partially restore SPINK1 function, present a novel genetic model of chronic pancreatitis.
DOI	10.1038/srep37200