RGD Reference Report - Impaired mucosal barrier function in the small intestine of the cystic fibrosis mouse. - Rat Genome Database

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Impaired mucosal barrier function in the small intestine of the cystic fibrosis mouse.

Authors: De Lisle, Robert C  Mueller, Racquel  Boyd, Megan 
Citation: De Lisle RC, etal., J Pediatr Gastroenterol Nutr. 2011 Oct;53(4):371-9. doi: 10.1097/MPG.0b013e318219c397.
RGD ID: 14349050
Pubmed: PMID:21970994   (View Abstract at PubMed)
PMCID: PMC3188387   (View Article at PubMed Central)
DOI: DOI:10.1097/MPG.0b013e318219c397   (Journal Full-text)


OBJECTIVES: The intestinal mucosal barrier protects the body from the large numbers of microbes that inhabit the intestines and the molecules they release. Intestinal barrier function is impaired in humans with cystic fibrosis (CF), including reduced activity of the lipopolysaccharide-detoxifying enzyme intestinal alkaline phosphatase (IAP) and increased permeability. The objective of this study was to determine the suitability of using the CF mouse to investigate intestinal barrier function, and whether interventions that are beneficial for the CF mouse intestinal phenotype (antibiotics or laxative), would improve barrier function. Also tested were the effects of exogenous IAP administration.
MATERIALS AND METHODS: The Cftr(tm1UNC) mouse was used. IAP expression (encoded by the murine Akp3 gene) was measured by quantitative reverse transcription-polymerase chain reaction and enzyme activity. Intestinal permeability was assessed by measuring rhodamine-dextran plasma levels following gavage.
RESULTS: CF mice had 40% Akp3 mRNA expression and 30% IAP enzyme activity, as compared with wild-type mice. Oral antibiotics and laxative treatments normalized Akp3 expression and IAP enzyme activity in the CF intestine. CF mice had a 5-fold greater transfer of rhodamine-dextran from gut lumen to blood. Antibiotic and laxative treatments reduced intestinal permeability in CF mice. Administration of exogenous purified IAP to CF mice reduced intestinal permeability to wild-type levels and reduced small intestinal bacterial overgrowth by >80%.
CONCLUSIONS: The CF mouse intestine has impaired mucosal barrier function, similar to human CF. Interventions that improve other aspects of the CF intestinal phenotype (antibiotics and laxative) also increase IAP activity and decrease intestinal permeability in CF mice. Exogenous IAP improve permeability and strongly reduce bacterial overgrowth in CF mice, suggesting this may be a useful therapy for CF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cystic fibrosis  IEP 14349050mRNA and protein:decreased expression:intestine:RGD 
cystic fibrosis  ISOAkp3 (Mus musculus)14349050mRNA and protein:decreased expression:intestine:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akp3  (alkaline phosphatase 3, intestine, not Mn requiring)

Genes (Mus musculus)
Akp3  (alkaline phosphatase 3, intestine, not Mn requiring)


Additional Information