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Article: Ileal mucosal bile acid absorption is increased in Cftr knockout mice

TitleIleal mucosal bile acid absorption is increased in Cftr knockout mice
Authors
KeywordsAnimal Tissue
Article
Brush Border
Controlled Study
Cystic Fibrosis
Diffusion
Gene Disruption
Gene Function
Heterozygosity
Homozygosity
Ileum Mucosa
Immunohistochemistry
Incubation Time
Intestine Absorption
Intestine Crypt
Isotope Labeling
Knockout Mouse
Malabsorption
Mouse
Nonhuman
Protein Function
Western Blotting
Wild Type
Issue Date2001
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcgastroenterol/
Citation
Bmc Gastroenterology, 2001, v. 1 How to Cite?
AbstractBackground: Excessive loss of bile acids in stool has been reported in patients with cystic fibrosis. Some data suggest that a defect in mucosal bile acid transport may be the mechanism of bile acid malabsorption in these individuals. However, the molecular basis of this defect is unknown. This study examines the expression of the ileal bile acid transporter protein (IBAT) and rates of diffusional (sodium independent) and active (sodium dependent) uptake of the radiolabeled bile acid taurocholate in mice with targeted disruption of the cftr gene. Methods: Wild-type, heterozygous cftr (+/-) and homozygous cftr (-/-) mice were studied. Five one-cm segments of terminal ileum were excised, everted and mounted onto thin stainless steel rods and incubated in buffer containing tracer 3H-taurocholate. Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein. Results: In all ileal segments, taurocholate uptake rates were fourfold higher in cftr (-/-) and two-fold higher in cftr (+/-) mice compared to wild-type mice. Passive uptake was not significantly higher in cftr (-/-) mice than in controls. IBAT protein was comparably increased. Immuno-staining revealed that the greatest increases occurred in the crypts of cftr (-/-) animals. Conclusions: In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/-) mice > cftr (+/-) > wild-type mice. These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border. Alternative mechanisms are proposed, such as impaired bile acid uptake caused by the thick mucus barrier in the distal small bowel, coupled with a direct negative regulatory role for cftr in IBAT function. © 2001 Stelzner et al; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/92528
ISSN
2015 Impact Factor: 2.101
2015 SCImago Journal Rankings: 0.999
PubMed Central ID
References

 

DC FieldValueLanguage
dc.contributor.authorStelzner, Men_HK
dc.contributor.authorSomasundaram, Sen_HK
dc.contributor.authorLee, SPen_HK
dc.contributor.authorKuver, Ren_HK
dc.date.accessioned2010-09-17T10:48:58Z-
dc.date.available2010-09-17T10:48:58Z-
dc.date.issued2001en_HK
dc.identifier.citationBmc Gastroenterology, 2001, v. 1en_HK
dc.identifier.issn1471-230Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/92528-
dc.description.abstractBackground: Excessive loss of bile acids in stool has been reported in patients with cystic fibrosis. Some data suggest that a defect in mucosal bile acid transport may be the mechanism of bile acid malabsorption in these individuals. However, the molecular basis of this defect is unknown. This study examines the expression of the ileal bile acid transporter protein (IBAT) and rates of diffusional (sodium independent) and active (sodium dependent) uptake of the radiolabeled bile acid taurocholate in mice with targeted disruption of the cftr gene. Methods: Wild-type, heterozygous cftr (+/-) and homozygous cftr (-/-) mice were studied. Five one-cm segments of terminal ileum were excised, everted and mounted onto thin stainless steel rods and incubated in buffer containing tracer 3H-taurocholate. Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein. Results: In all ileal segments, taurocholate uptake rates were fourfold higher in cftr (-/-) and two-fold higher in cftr (+/-) mice compared to wild-type mice. Passive uptake was not significantly higher in cftr (-/-) mice than in controls. IBAT protein was comparably increased. Immuno-staining revealed that the greatest increases occurred in the crypts of cftr (-/-) animals. Conclusions: In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/-) mice > cftr (+/-) > wild-type mice. These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border. Alternative mechanisms are proposed, such as impaired bile acid uptake caused by the thick mucus barrier in the distal small bowel, coupled with a direct negative regulatory role for cftr in IBAT function. © 2001 Stelzner et al; licensee BioMed Central Ltd.en_HK
dc.languageengen_HK
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcgastroenterol/en_HK
dc.relation.ispartofBMC Gastroenterologyen_HK
dc.subjectAnimal Tissueen_HK
dc.subjectArticleen_HK
dc.subjectBrush Borderen_HK
dc.subjectControlled Studyen_HK
dc.subjectCystic Fibrosisen_HK
dc.subjectDiffusionen_HK
dc.subjectGene Disruptionen_HK
dc.subjectGene Functionen_HK
dc.subjectHeterozygosityen_HK
dc.subjectHomozygosityen_HK
dc.subjectIleum Mucosaen_HK
dc.subjectImmunohistochemistryen_HK
dc.subjectIncubation Timeen_HK
dc.subjectIntestine Absorptionen_HK
dc.subjectIntestine Crypten_HK
dc.subjectIsotope Labelingen_HK
dc.subjectKnockout Mouseen_HK
dc.subjectMalabsorptionen_HK
dc.subjectMouseen_HK
dc.subjectNonhumanen_HK
dc.subjectProtein Functionen_HK
dc.subjectWestern Blottingen_HK
dc.subjectWild Typeen_HK
dc.titleIleal mucosal bile acid absorption is increased in Cftr knockout miceen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SP: sumlee@hku.hken_HK
dc.identifier.authorityLee, SP=rp01351en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1471-230X-1-10en_HK
dc.identifier.pmid11696242-
dc.identifier.pmcidPMC59644-
dc.identifier.scopuseid_2-s2.0-2942618393en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2942618393&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume1en_HK
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridStelzner, M=21637112500en_HK
dc.identifier.scopusauthoridSomasundaram, S=55390916900en_HK
dc.identifier.scopusauthoridLee, SP=7601417497en_HK
dc.identifier.scopusauthoridKuver, R=6701723533en_HK

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