Document Detail

Knockout mouse models for intestinal electrolyte transporters and regulatory PDZ adaptors: new insights into cystic fibrosis, secretory diarrhoea and fructose-induced hypertension.
MedLine Citation:
PMID:  18931049     Owner:  NLM     Status:  MEDLINE    
Knockout mouse models have provided key insights into the physiological significance of many intestinal electrolyte transporters. This review has selected three examples to highlight the importance of knockout mouse technology in unravelling complex regulatory relationships important for the understanding of human diseases. Genetic ablation of the cystic fibrosis transmembrane conductance regulator (CFTR) has created one of the most useful mouse models for understanding intestinal transport. Recent work has provided an understanding of the key role of the CFTR anion channel in the regulation of HCO(3)(-) secretion, and the important consequences that a defect in HCO(3)(-) output may have on the viscoelastic properties of mucus, on lipid absorption and on male and female reproductive function. The regulation of CFTR activity, and also that of the intestinal salt absorptive transporter NHE3, occurs via the formation of PSD95-Drosophila homologue Discs-large-tight junction protein ZO-1 (PDZ) adaptor protein-mediated multiprotein complexes. The recent generation of knockout mice for three members of the sodium-hydrogen regulatory factor (NHERF) family of PDZ adaptor proteins, namely NHERF1 (EBP50), NHERF2 (E3KARP) and NHERF3 (PDZK1), has helped to explain why NHERF1 is essential for both normal and mutant CFTR function. In addition, they have provided new insight into the molecular mechanisms of secretory diarrhoeas. Genetic ablation of members of the recently discovered Slc26 anion transporter gene family not only reproduced the phenotype of the genetic diseases that led to the discovery of the gene family, but also resulted in new insights into complex human diseases such as secretory diarrhoea, fructose-induced hypertension and urolithiasis.
Ursula Seidler; Anurag Singh; Mingmin Chen; Ayhan Cinar; Oliver Bachmann; Wen Zheng; Jian Wang; Sunil Yeruva; Brigitte Riederer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2008-10-17
Journal Detail:
Title:  Experimental physiology     Volume:  94     ISSN:  1469-445X     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-15     Completed Date:  2009-04-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  175-9     Citation Subset:  IM    
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
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MeSH Terms
Bicarbonates / metabolism
Biological Transport / physiology
Cystic Fibrosis / genetics,  metabolism*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics,  metabolism
Diarrhea / genetics,  metabolism*
Disease Models, Animal
Epithelial Cells / metabolism,  pathology
Hypertension / genetics,  metabolism*
Intracellular Signaling Peptides and Proteins / genetics,  metabolism*
Lipolysis / physiology
Mice, Inbred CFTR
Mice, Knockout
Phosphoproteins / genetics,  metabolism*
Sodium-Hydrogen Antiporter / genetics,  metabolism*
Reg. No./Substance:
0/Bicarbonates; 0/Intracellular Signaling Peptides and Proteins; 0/PDZK1 protein, mouse; 0/Phosphoproteins; 0/Sodium-Hydrogen Antiporter; 0/sodium-hydrogen exchanger 3; 0/sodium-hydrogen exchanger regulatory factor; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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