A mouse model for the delta F508 allele of cystic fibrosis
The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508...
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| Veröffentlicht in: | The Journal of clinical investigation 1995-10, Vol.96 (4), p.2051-2064 |
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| container_title | The Journal of clinical investigation |
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| creator | Zeiher, B G Eichwald, E Zabner, J Smith, J J Puga, A P McCray, Jr, P B Capecchi, M R Welsh, M J Thomas, K R |
| description | The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508 mutation into the mouse CFTR gene. Affected epithelia from homozygous delta F508 mice lacked CFTR in the apical membrane and were Cl-impermeable. These abnormalities are the same as those observed in patients with delta F508 and suggest that these mice have the same cellular defect. 40% of homozygous delta F508 animals survived into adulthood and displayed several abnormalities found in human disease and in CFTR null mice. These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the delta F508 defect. |
| doi_str_mv | 10.1172/JCI118253 |
| format | Article |
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The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508 mutation into the mouse CFTR gene. Affected epithelia from homozygous delta F508 mice lacked CFTR in the apical membrane and were Cl-impermeable. These abnormalities are the same as those observed in patients with delta F508 and suggest that these mice have the same cellular defect. 40% of homozygous delta F508 animals survived into adulthood and displayed several abnormalities found in human disease and in CFTR null mice. 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These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the delta F508 defect.</description><subject>Alleles</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Cystic Fibrosis - genetics</subject><subject>Cystic Fibrosis - pathology</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator - genetics</subject><subject>Digestive System - metabolism</subject><subject>Digestive System - pathology</subject><subject>Disease Models, Animal</subject><subject>Electrolytes - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Pancreatic Ducts - metabolism</subject><subject>RNA, Messenger - analysis</subject><issn>0021-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUE1LAzEQzUGptXrwBwg5CR5WJ1-bRPBQih-Vghc9h2w2sSvZbt1shf57Iy1FLzMD897Mew-hCwI3hEh6-zKbE6KoYEdoDEBJoSVTJ-g0pU8AwrngIzSSogTQeozuprjtNsnnWvuIQ9fjYelxngeLHwUobGP00eMuYLdNQ-NwaKq-S006Q8fBxuTP932C3h8f3mbPxeL1aT6bLgrHQQ8FEURUVjJRBSqzLilpSS2RofYMPKlUCFoFBxB4xQVlFQ8lsFrWrgQORLAJut_dXW-q1tfOr4beRrPum9b2W9PZxvzfrJql-ei-DVFCcZ75V3t-331tfBpM2yTnY7Qrn60bKQXXWtMMvN4BXfaXeh8OPwiY32zNIduMvfwr6oDcB8t-AC7_dMA</recordid><startdate>19951001</startdate><enddate>19951001</enddate><creator>Zeiher, B G</creator><creator>Eichwald, E</creator><creator>Zabner, J</creator><creator>Smith, J J</creator><creator>Puga, A P</creator><creator>McCray, Jr, P B</creator><creator>Capecchi, M R</creator><creator>Welsh, M J</creator><creator>Thomas, K R</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19951001</creationdate><title>A mouse model for the delta F508 allele of cystic fibrosis</title><author>Zeiher, B G ; Eichwald, E ; Zabner, J ; Smith, J J ; Puga, A P ; McCray, Jr, P B ; Capecchi, M R ; Welsh, M J ; Thomas, K R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-1515ba735bf2782577262a17fde30e1b8ff98fc00f4b4523b4f603d7dc6040153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Cystic Fibrosis - genetics</topic><topic>Cystic Fibrosis - pathology</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator - genetics</topic><topic>Digestive System - metabolism</topic><topic>Digestive System - pathology</topic><topic>Disease Models, Animal</topic><topic>Electrolytes - metabolism</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Pancreatic Ducts - metabolism</topic><topic>RNA, Messenger - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeiher, B G</creatorcontrib><creatorcontrib>Eichwald, E</creatorcontrib><creatorcontrib>Zabner, J</creatorcontrib><creatorcontrib>Smith, J J</creatorcontrib><creatorcontrib>Puga, A P</creatorcontrib><creatorcontrib>McCray, Jr, P B</creatorcontrib><creatorcontrib>Capecchi, M R</creatorcontrib><creatorcontrib>Welsh, M J</creatorcontrib><creatorcontrib>Thomas, K R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeiher, B G</au><au>Eichwald, E</au><au>Zabner, J</au><au>Smith, J J</au><au>Puga, A P</au><au>McCray, Jr, P B</au><au>Capecchi, M R</au><au>Welsh, M J</au><au>Thomas, K R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mouse model for the delta F508 allele of cystic fibrosis</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1995-10-01</date><risdate>1995</risdate><volume>96</volume><issue>4</issue><spage>2051</spage><epage>2064</epage><pages>2051-2064</pages><issn>0021-9738</issn><abstract>The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508 mutation into the mouse CFTR gene. Affected epithelia from homozygous delta F508 mice lacked CFTR in the apical membrane and were Cl-impermeable. These abnormalities are the same as those observed in patients with delta F508 and suggest that these mice have the same cellular defect. 40% of homozygous delta F508 animals survived into adulthood and displayed several abnormalities found in human disease and in CFTR null mice. These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the delta F508 defect.</abstract><cop>United States</cop><pmid>7560099</pmid><doi>10.1172/JCI118253</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of clinical investigation, 1995-10, Vol.96 (4), p.2051-2064 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Alleles Animals Base Sequence Cystic Fibrosis - genetics Cystic Fibrosis - pathology Cystic Fibrosis Transmembrane Conductance Regulator - genetics Digestive System - metabolism Digestive System - pathology Disease Models, Animal Electrolytes - metabolism Humans Mice Mice, Inbred C57BL Molecular Sequence Data Mutation Pancreatic Ducts - metabolism RNA, Messenger - analysis |
| title | A mouse model for the delta F508 allele of cystic fibrosis |
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