Potential genetic modifiers of the cystic fibrosis intestinal inflammatory phenotype on mouse chromosomes 1, 9, and 10

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dc.contributor.author Oxana Norkina en_US
dc.contributor.author Robert De Lisle en_US
dc.date.accessioned 2009-05-05T16:14:28Z
dc.date.available 2005 - en_US
dc.date.available 2009-05-05T16:14:28Z
dc.date.issued 2008-05-09 en_US
dc.identifier.citation Oxana Norkina;Robert De Lisle: Potential genetic modifiers of the cystic fibrosis intestinal inflammatory phenotype on mouse chromosomes 1, 9, and 10. BMC Genet 2005, 6(1):29. en_US
dc.identifier.uri http://www.biomedcentral.com/1471-2156/6/29 en_US
dc.identifier.uri http://hdl.handle.net/2271/598
dc.description.abstract BACKGROUND:Although cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the severity of disease is highly variable indicating the influence of modifier genes. The intestines of Cftr deficient mice (CF mice: Cftrtm1Unc) are prone to obstruction by excessive mucus accumulation and are used as a model of meconium ileus and distal intestinal obstruction syndrome. This phenotype is strongly dependent on the genetic background of the mice. On the C57Bl/6 background, the majority of CF mice cannot survive on solid mouse chow, have inflammation of the small intestine, and are about 30% smaller than wild type littermates. In this work potential modifier loci of the CF intestinal phenotype were identified.RESULTS:CF mice on a mixed genetic background (95% C57Bl/6 and 5% 129Sv) were compared to CF mice congenic on the C57Bl/6 background for several parameters of the intestinal CF phenotype. CF mice on the mixed background exhibit significantly greater survival when fed dry mouse chow, have reduced intestinal inflammation as measured by quantitative RT-PCR for marker genes, have near normal body weight gain, and have reduced mucus accumulation in the intestinal crypts. There was an indication of a gender effect for body weight gain: males did not show a significant improvement at 4 weeks of age, but were of normal weight at 8 weeks, while females showed improvement at both 4 and 8 weeks. By a preliminary genome-wide PCR allele scanning, three regions were found to be potentially associated with the milder phenotype. One on chr.1, defined by marker D1Mit36, one on chr. 9 defined by marker D9Mit90, and one on chr. 10, defined by marker D10Mit14.CONCLUSION:Potential modifier regions were found that have a positive impact on the inflammatory phenotype of the CF mouse small intestine and animal survival. Identification of polymorphisms in specific genes in these regions should provide important new information about genetic modifiers of the CF intestinal phenotype. en_US
dc.format.extent 1678612 bytes
dc.format.extent 2910 bytes
dc.format.extent 12055 bytes
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dc.format.extent 43 bytes
dc.format.mimetype application/pdf
dc.format.mimetype text/plain
dc.format.mimetype application/octet-stream
dc.format.mimetype application/octet-stream
dc.format.mimetype application/octet-stream
dc.language en en_US
dc.language.iso en_US
dc.publisher BioMedCentral en_US
dc.relation.ispartof 1471-2156 en_US
dc.relation.hasversion http://www.biomedcentral.com/content/pdf/1471-2156-6-29.pdf en_US
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.subject.mesh Animals en_US
dc.subject.mesh Cnidaria/classification/genetics en_US
dc.subject.mesh DNA, Ribosomal/genetics en_US
dc.subject.mesh Hydrozoa/ classification/genetics/growth & development en_US
dc.subject.mesh Life Cycle Stages en_US
dc.subject.mesh Phylogeny en_US
dc.subject.mesh RNA, Ribosomal, 18S/genetics en_US
dc.title Potential genetic modifiers of the cystic fibrosis intestinal inflammatory phenotype on mouse chromosomes 1, 9, and 10 en_US
dc.type article en_US
dc.date.captured 2009-04-27 en_US
dc.identifier.doi doi:10.1186/1471-2156-6-29 en_US
dc.identifier.pmid 18471296 en_US

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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