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Mutations at splice junctions often cause exon skipping, short deletions, or insertions in the mature mRNA, underlying one common molecular mechanism of genetic diseases. Using N-ethyl-N-nitrosourea, a novel recessive mutation named <jats:italic>seal<\/jats:italic> was produced, associated with fragile bones and susceptibility to fractures (spine and limbs). A single nucleotide transversion (T\u2009\u2192\u2009A) at the second position of intron 36 of the <jats:italic>Col1a1<\/jats:italic> gene, encoding the type I collagen, \u03b11 chain, was responsible for the phenotype. <jats:italic>Col1a1<\/jats:italic><jats:sup>\n                  <jats:italic>seal<\/jats:italic>\n                <\/jats:sup> mRNA expression occurred at greatly reduced levels compared to the wild-type transcript, resulting in reduced and aberrant collagen fibers in tibiae of <jats:italic>seal<\/jats:italic> homozygous mice. Unexpectedly, splicing of <jats:italic>Col1a1<\/jats:italic><jats:sup>\n                  <jats:italic>seal<\/jats:italic>\n                <\/jats:sup> mRNA followed the normal pattern despite the presence of the donor splice site mutation, likely due to the action of a putative intronic splicing enhancer present in intron 25, which appeared to function redundantly with the splice donor site of intron 36. <jats:italic>Seal<\/jats:italic> mice represent a model of human osteogenesis imperfecta, and reveal a previously unknown mechanism for splicing \u201crescue.\u201d<\/jats:p>","DOI":"10.1038\/s41598-017-10343-9","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T13:56:07Z","timestamp":1505138167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-1872","authenticated-orcid":false,"given":"Koichi","family":"Tabeta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Arimatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Yokoji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Amizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoka","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine","family":"Crozat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Maekawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayuri","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Ida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Kaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasper","family":"Hoebe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinji","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromasa","family":"Yoshie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhisa","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Marie Y.","family":"Moresco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Beutler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"10343_CR1","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1126\/science.170.3962.1096","volume":"170","author":"JG Nold","year":"1970","unstructured":"Nold, J. 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