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We previously reported that mice lacking\n                    <jats:italic>Spink3<\/jats:italic>\n                    , the murine homologue of human\n                    <jats:italic>SPINK1<\/jats:italic>\n                    , 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\n                    <jats:italic>SPINK1<\/jats:italic>\n                    gene on the X chromosome using Cre-\n                    <jats:italic>lox<\/jats:italic>\n                    P technology and thus generated transgenic mice termed \u201c\n                    <jats:italic>X-SPINK1<\/jats:italic>\n                    \u201c. Consistent with the fact that one of the two X chromosomes is randomly inactivated,\n                    <jats:italic>X-SPINK1<\/jats:italic>\n                    mice exhibit mosaic pattern of\n                    <jats:italic>SPINK1<\/jats:italic>\n                    expression. Crossing of\n                    <jats:italic>X-SPINK1<\/jats:italic>\n                    mice with\n                    <jats:italic>Spink3<\/jats:italic>\n                    <jats:sup>\n                      +\n                      <jats:italic>\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    mice rescued perinatal lethality, but the resulting\n                    <jats:italic>Spink3<\/jats:italic>\n                    <jats:sup>\n                      \u2212\n                      <jats:italic>\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    <jats:italic>;XX<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>SPINK1<\/jats:italic>\n                    <\/jats:sup>\n                    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\n                    <jats:italic>Spink3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>;XX<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>SPINK1<\/jats:italic>\n                    <\/jats:sup>\n                    mice, in which this method has been applied to partially restore SPINK1 function, present a novel genetic model of chronic pancreatitis.\n                  <\/jats:p>","DOI":"10.1038\/srep37200","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T05:10:03Z","timestamp":1479186603000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome"],"prefix":"10.1038","volume":"6","author":[{"given":"Kazuya","family":"Sakata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimi","family":"Araki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyasu","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Nishina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Komazawa-Sakon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Murai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace E.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chigure","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Notohara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna S.","family":"Gukovskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Gukovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken-ichi","family":"Yamamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Baba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Ohmuraya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,15]]},"reference":[{"key":"BFsrep37200_CR1","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1136\/gut.2003.015511","volume":"53","author":"DC Whitcomb","year":"2004","unstructured":"Whitcomb, D. 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