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Article: Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA
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TitleIncomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA
 
AuthorsRozmahel, R2 3
Gyömörey, K1 3
Plyte, S3
Nguyen, V3
Wilschanski, M3
Durie, P2 3
Bear, CE1 3
Tsui, LC2 3
 
Issue Date1997
 
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
CitationHuman Molecular Genetics, 1997, v. 6 n. 7, p. 1153-1162 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/6.7.1153
 
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.
 
ISSN0964-6906
2012 Impact Factor: 7.692
2012 SCImago Journal Rankings: 4.103
 
Other Identifiershttp://hmg.oxfordjournals.org/cgi/reprint/6/7/1153
 
DOIhttp://dx.doi.org/10.1093/hmg/6.7.1153
 
ISI Accession Number IDWOS:A1997XH93200024
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorRozmahel, R
 
dc.contributor.authorGyömörey, K
 
dc.contributor.authorPlyte, S
 
dc.contributor.authorNguyen, V
 
dc.contributor.authorWilschanski, M
 
dc.contributor.authorDurie, P
 
dc.contributor.authorBear, CE
 
dc.contributor.authorTsui, LC
 
dc.date.accessioned2007-09-12T03:51:18Z
 
dc.date.available2007-09-12T03:51:18Z
 
dc.date.issued1997
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationHuman Molecular Genetics, 1997, v. 6 n. 7, p. 1153-1162 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/6.7.1153
 
dc.identifier.doihttp://dx.doi.org/10.1093/hmg/6.7.1153
 
dc.identifier.epage1162
 
dc.identifier.isiWOS:A1997XH93200024
 
dc.identifier.issn0964-6906
2012 Impact Factor: 7.692
2012 SCImago Journal Rankings: 4.103
 
dc.identifier.issue7
 
dc.identifierhttp://hmg.oxfordjournals.org/cgi/reprint/6/7/1153
 
dc.identifier.pmid9215687
 
dc.identifier.scopuseid_2-s2.0-0030799599
 
dc.identifier.spage1153
 
dc.identifier.urihttp://hdl.handle.net/10722/44318
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofHuman Molecular Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshCystic fibrosis - genetics
 
dc.subject.meshCystic fibrosis transmembrane conductance regulator - deficiency - genetics - metabolism
 
dc.subject.meshElectrophysiology
 
dc.subject.meshForskolin - pharmacology
 
dc.subject.meshIntestines - drug effects - physiology
 
dc.titleIncomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA
 
dc.typeArticle
 
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<contributor.author>Nguyen, V</contributor.author>
<contributor.author>Wilschanski, M</contributor.author>
<contributor.author>Durie, P</contributor.author>
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<description.abstract>We 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 &apos;knock-in&apos; 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.</description.abstract>
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Author Affiliations
  1. University of Toronto Faculty of Medicine
  2. University of Toronto
  3. Hospital for Sick Children University of Toronto