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A Cftr knockout (Cftr KO) mouse expressing mutants of human CFTR would advance <jats:italic>in vivo<\/jats:italic> testing of new modulators. A bacterial artificial chromosome (BAC) carrying the complete <jats:italic>hCFTR<\/jats:italic> gene including regulatory elements within 40.1\u2009kb of DNA 5\u2032 and 25\u2009kb of DNA 3\u2032 to the gene was used to generate founder mice expressing hCFTR. Whole genome sequencing indicated a single integration site on mouse chromosome 8 (8qB2) with ~6 gene copies. hCFTR+ offspring were bred to murine Cftr KO mice, producing hCFTR+\/mCftr\u2212 (H+\/m\u2212) mice, which had normal survival, growth and goblet cell function as compared to wild-type (WT) mice. Expression studies showed hCFTR protein and transcripts in tissues typically expressing mCftr. Functionally, nasal potential difference and large intestinal short-circuit (I<jats:sub>sc<\/jats:sub>) responses to cAMP stimulation were similar in magnitude to WT mice, whereas small intestinal cAMP \u0394I<jats:sub>sc<\/jats:sub> responses were reduced. A BAC transgenic mouse with functional hCFTR under control of its regulatory elements has been developed to enable the generation of mouse models of hCFTR mutations by gene editing for <jats:italic>in vivo<\/jats:italic> testing of new CF therapies.<\/jats:p>","DOI":"10.1038\/s41598-019-48105-4","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T10:02:36Z","timestamp":1565776956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A BAC Transgene Expressing Human CFTR under Control of Its Regulatory Elements Rescues Cftr Knockout Mice"],"prefix":"10.1038","volume":"9","author":[{"given":"Lara R.","family":"Gawenis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Hodges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"McHugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana M.","family":"Valerio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Miron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin U.","family":"Cotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy M.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee M.","family":"Strubberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin E.","family":"Gillen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Mutolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kotzamanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell L.","family":"Drumm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4938-6261","authenticated-orcid":false,"given":"Lane L.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"key":"48105_CR1","doi-asserted-by":"publisher","first-page":"L529","DOI":"10.1152\/ajplung.00465.2017","volume":"314","author":"M Harutyunyan","year":"2018","unstructured":"Harutyunyan, M. et al. 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