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Physiol. Genomics 24: 124-132, 2006. First published November 8, 2005; doi:10.1152/physiolgenomics.00133.2005
1094-8341/06 $8.00
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Received 8 June 2005; accepted in final form 4 November 2005.
Physiological Genomics 24:124-132 (2006)
1094-8341/05 $8.00 © 2006 American Physiological Society

Gene expression profiling of gastrin target genes in parietal cells

Renu N. Jain1, Cynthia S. Brunkan1, Catherine S. Chew2 and Linda C. Samuelson1

1 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan
2 Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia

Previous studies demonstrated that mice with a null mutation in the gene encoding the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell proteins involved in gastric acid secretion showed reduced abundance in the GAS-KO stomach, including H+,K+-ATPase {alpha}- and ß-subunits, KCNQ1 potassium channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by gastrin infusion for 1 wk. Although mRNA and protein levels of LIM and SH3 domain-containing protein-1 (LASP-1) were not greatly changed in the mutant, there was a marked reduction in phosphorylation, consistent with its proposed role as a cAMP signal adaptor protein associated with acid secretion. A more comprehensive analysis of parietal cell gene expression in GAS-KO mice was performed using the Affymetrix U74AV2 chip with RNA from parietal cells purified by flow cytometry to >90%. Comparison of gene expression in GAS-KO and wild-type mice identified 47 transcripts that differed by greater than or equal to twofold, suggesting that gastrin affects parietal cell gene expression in a specific manner. The differentially expressed genes included several genes in signaling pathways, with a substantial number (20%) known to be target genes for Wnt and Myc.

stomach; gastric acid secretion; gene expression microarray; gastrin-deficient mice; fundic mucosa




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