Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome

• DOI: 10.1038/srep37200
• Publication Date: 2016-11-15T10:10:03Z
• Authors: Kazuya Sakata; Kimi Araki; Hiroyasu Nakano; Takashi Nishina; Sachiko Komazawa-...; Shin Murai; Grace E. Lee; Daisuke Hashimoto; Chigure Suzuki; Yasuo Uchiyama; Kenji Notohara; Anna S. Gukovskaya; Ilya Gukovsky; Ken-ichi Yamamura; Hideo Baba; Masaki Ohmuraya
• Keywords: Gain of function

Abstract 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 , murine homologue die perinatally due to massive pancreatic acinar cell death, precluding investigation effects deficiency. To circumvent perinatal lethality, we have developed a novel method integrate on X chromosome using Cre- lox P technology and thus generated transgenic termed “ X-SPINK1 “. Consistent fact one two chromosomes is randomly inactivated, exhibit mosaic pattern expression. Crossing + / − rescued resulting ;XX spontaneous pancreatitis characterized by inflammation fibrosis. results show essential for survival can be expressing this chromosome. −/− mice, in which has been applied partially restore function, present genetic model pancreatitis.