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Article: Detection of modifier loci influencing the lung phenotype of cystic fibrosis knockout mice

TitleDetection of modifier loci influencing the lung phenotype of cystic fibrosis knockout mice
Authors
Issue Date2002
PublisherSpringer New York LLC. The Journal's web site is located at http://link.springer.de/link/service/journals/00335/
Citation
Mammalian Genome, 2002, v. 13 n. 11, p. 605-613 How to Cite?
Abstract
The variable severity of lung disease associated with cystic fibrosis (CF) cannot be explained by the genotype of the cystic fibrosis transmembrane conductance regulator (CFTR) locus alone. Lung disease has been reported in a congenic CF mouse model of C57BL/6J genetic background (B6 CF), in the absence of detectable infection, but not in CF mice of mixed genetic background, nor in wild-type animals maintained in identical environments. In this report, studies are presented to show that the same CF mutation in mice of a BALB/c background (BALB CF) results in minimal lung disease. By 12 weeks of age B6 CF mice developed a lung disease consisting of mononuclear cell interstitial infiltrate and fibrosis, and BALB CF or littermate control mice developed minimal histopathology. Therefore, it is possible to identify the chromosomal locations of genes that can contribute to the susceptibility to lung disease in B6 CF mice compared with BALB CF mice by means of a quantitative trait loci (QTL) mapping strategy based on the variable histology of the (B6 x BALB) F2 CF mice. Significant linkage of the fibrotic lung phenotype was detected for a region on Chromosome (Chr) 6, defined by markers D6Mit194 to D6Mit201, and suggestive linkage was found for regions on Chr 1, 2, 10, and 17. Additional loci, suggestive of linkage, were also detected for the interstitial thickening phenotype. Most of these putative loci are specific to the sex of the animals. These results suggest that multiple genes can influence the severity of CF lung disease in mice.
Persistent Identifierhttp://hdl.handle.net/10722/44376
ISSN
2013 Impact Factor: 2.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHaston, CKen_HK
dc.contributor.authorMcKerlie, Cen_HK
dc.contributor.authorNewbigging, Sen_HK
dc.contributor.authorCorey, Men_HK
dc.contributor.authorRozmahel, Ren_HK
dc.contributor.authorTsui, LCen_HK
dc.date.accessioned2007-09-12T03:52:21Z-
dc.date.available2007-09-12T03:52:21Z-
dc.date.issued2002en_HK
dc.identifier.citationMammalian Genome, 2002, v. 13 n. 11, p. 605-613en_HK
dc.identifier.issn0938-8990en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44376-
dc.description.abstractThe variable severity of lung disease associated with cystic fibrosis (CF) cannot be explained by the genotype of the cystic fibrosis transmembrane conductance regulator (CFTR) locus alone. Lung disease has been reported in a congenic CF mouse model of C57BL/6J genetic background (B6 CF), in the absence of detectable infection, but not in CF mice of mixed genetic background, nor in wild-type animals maintained in identical environments. In this report, studies are presented to show that the same CF mutation in mice of a BALB/c background (BALB CF) results in minimal lung disease. By 12 weeks of age B6 CF mice developed a lung disease consisting of mononuclear cell interstitial infiltrate and fibrosis, and BALB CF or littermate control mice developed minimal histopathology. Therefore, it is possible to identify the chromosomal locations of genes that can contribute to the susceptibility to lung disease in B6 CF mice compared with BALB CF mice by means of a quantitative trait loci (QTL) mapping strategy based on the variable histology of the (B6 x BALB) F2 CF mice. Significant linkage of the fibrotic lung phenotype was detected for a region on Chromosome (Chr) 6, defined by markers D6Mit194 to D6Mit201, and suggestive linkage was found for regions on Chr 1, 2, 10, and 17. Additional loci, suggestive of linkage, were also detected for the interstitial thickening phenotype. Most of these putative loci are specific to the sex of the animals. These results suggest that multiple genes can influence the severity of CF lung disease in mice.en_HK
dc.languageengen_HK
dc.publisherSpringer New York LLC. The Journal's web site is located at http://link.springer.de/link/service/journals/00335/en_HK
dc.relation.ispartofMammalian Genomeen_HK
dc.rightsThe original publication is available at www.springerlink.comen_HK
dc.subject.meshCystic fibrosis - genetics - metabolism - pathologyen_HK
dc.subject.meshDisease models, animalen_HK
dc.subject.meshLung - metabolism - pathologyen_HK
dc.subject.meshNeutrophils - metabolismen_HK
dc.subject.meshQuantitative trait locien_HK
dc.titleDetection of modifier loci influencing the lung phenotype of cystic fibrosis knockout miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0938-8990&volume=13&issue=11&spage=605&epage=613&date=2002&atitle=Detection+of+modifier+loci+influencing+the+lung+phenotype+of+cystic+fibrosis+knockout+miceen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.natureabstracten_HK
dc.identifier.doi10.1007/s00335-002-2190-7en_HK
dc.identifier.pmid12461645en_HK
dc.identifier.scopuseid_2-s2.0-0036855652en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036855652&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume13en_HK
dc.identifier.issue11en_HK
dc.identifier.spage605en_HK
dc.identifier.epage613en_HK
dc.identifier.isiWOS:000179616200001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHaston, CK=6602880337en_HK
dc.identifier.scopusauthoridMcKerlie, C=35993902900en_HK
dc.identifier.scopusauthoridNewbigging, S=7801637431en_HK
dc.identifier.scopusauthoridCorey, M=7005819978en_HK
dc.identifier.scopusauthoridRozmahel, R=6701510561en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK

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