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

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TitleDetection of modifier loci influencing the lung phenotype of cystic fibrosis knockout mice
AuthorsHaston, CK2 3 5
McKerlie, C5
Newbigging, S5
Corey, M5
Rozmahel, R3 4 5
Tsui, LC1 3 5
Issue Date2002
PublisherSpringer New York LLC. The Journal's web site is located at http://link.springer.de/link/service/journals/00335/
CitationMammalian Genome, 2002, v. 13 n. 11, p. 605-613 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00335-002-2190-7
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.
ISSN0938-8990
2011 Impact Factor: 2.887
2011 SCImago Journal Rankings: 0.440
DOIhttp://dx.doi.org/10.1007/s00335-002-2190-7
ISI Accession Number IDWOS:000179616200001
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorHaston, CK
dc.contributor.authorMcKerlie, C
dc.contributor.authorNewbigging, S
dc.contributor.authorCorey, M
dc.contributor.authorRozmahel, R
dc.contributor.authorTsui, LC
dc.date.accessioned2007-09-12T03:52:21Z
dc.date.available2007-09-12T03:52:21Z
dc.date.issued2002
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.
dc.description.natureabstract
dc.identifier.citationMammalian Genome, 2002, v. 13 n. 11, p. 605-613 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00335-002-2190-7
dc.identifier.doihttp://dx.doi.org/10.1007/s00335-002-2190-7
dc.identifier.epage613
dc.identifier.isiWOS:000179616200001
dc.identifier.issn0938-8990
2011 Impact Factor: 2.887
2011 SCImago Journal Rankings: 0.440
dc.identifier.issue11
dc.identifier.openurl
dc.identifier.pmid12461645
dc.identifier.scopuseid_2-s2.0-0036855652
dc.identifier.spage605
dc.identifier.urihttp://hdl.handle.net/10722/44376
dc.identifier.volume13
dc.languageeng
dc.publisherSpringer New York LLC. The Journal's web site is located at http://link.springer.de/link/service/journals/00335/
dc.publisher.placeUnited States
dc.relation.ispartofMammalian Genome
dc.relation.referencesReferences in Scopus
dc.rightsThe original publication is available at www.springerlink.com
dc.subject.meshCystic fibrosis - genetics - metabolism - pathology
dc.subject.meshDisease models, animal
dc.subject.meshLung - metabolism - pathology
dc.subject.meshNeutrophils - metabolism
dc.subject.meshQuantitative trait loci
dc.titleDetection of modifier loci influencing the lung phenotype of cystic fibrosis knockout mice
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Meakins-Christie Laboratories
  3. University of Toronto
  4. University of Alabama
  5. Hospital for Sick Children, Toronto