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Article: Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA

TitleIncomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA
Authors
Issue Date1997
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 1997, v. 6 n. 7, p. 1153-1162 How to Cite?
AbstractWe have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue-specific expression and regulation of CFTR function when animal models are used in gene therapy studies.
Persistent Identifierhttp://hdl.handle.net/10722/44318
ISSN
2023 Impact Factor: 3.1
2023 SCImago Journal Rankings: 1.602
Other Identifiers
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRozmahel, Ren_HK
dc.contributor.authorGyömörey, Ken_HK
dc.contributor.authorPlyte, Sen_HK
dc.contributor.authorNguyen, Ven_HK
dc.contributor.authorWilschanski, Men_HK
dc.contributor.authorDurie, Pen_HK
dc.contributor.authorBear, CEen_HK
dc.contributor.authorTsui, LCen_HK
dc.date.accessioned2007-09-12T03:51:18Z-
dc.date.available2007-09-12T03:51:18Z-
dc.date.issued1997en_HK
dc.identifierhttp://hmg.oxfordjournals.org/cgi/reprint/6/7/1153en_HK
dc.identifier.citationHuman Molecular Genetics, 1997, v. 6 n. 7, p. 1153-1162en_HK
dc.identifier.issn0964-6906en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44318-
dc.description.abstractWe have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue-specific expression and regulation of CFTR function when animal models are used in gene therapy studies.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Molecular Geneticsen_HK
dc.subject.meshCystic fibrosis - geneticsen_HK
dc.subject.meshCystic fibrosis transmembrane conductance regulator - deficiency - genetics - metabolismen_HK
dc.subject.meshElectrophysiologyen_HK
dc.subject.meshForskolin - pharmacologyen_HK
dc.subject.meshIntestines - drug effects - physiologyen_HK
dc.titleIncomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNAen_HK
dc.typeArticleen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1093/hmg/6.7.1153en_HK
dc.identifier.pmid9215687en_HK
dc.identifier.scopuseid_2-s2.0-0030799599en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030799599&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1153en_HK
dc.identifier.epage1162en_HK
dc.identifier.isiWOS:A1997XH93200024-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridRozmahel, R=6701510561en_HK
dc.identifier.scopusauthoridGyömörey, K=6507537513en_HK
dc.identifier.scopusauthoridPlyte, S=15740317900en_HK
dc.identifier.scopusauthoridNguyen, V=7203068946en_HK
dc.identifier.scopusauthoridWilschanski, M=6701812857en_HK
dc.identifier.scopusauthoridDurie, P=7005360997en_HK
dc.identifier.scopusauthoridBear, CE=7006718679en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.issnl0964-6906-

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