HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Zhou, D. Articles by Haddad, G. G. Search for Related Content PubMed PubMed Citation Articles by Zhou, D. Articles by Haddad, G. G.

Na⁺/H⁺ exchanger 1 deficiency alters gene expression in mouse brain

¹ Department of Pediatrics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461
² Department of Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461

Na⁺/H⁺ exchanger 1 (NHE1) is well known to function as a major regulator of intracellular pH (pH_i). It is activated by low pH_i and exchanges extracellular Na⁺ for intracellular H⁺ to maintain cellular homeostasis. Despite the fact that we now have evidence suggesting other roles for NHE1, there has been no comprehensive study investigating its role as a signaling molecule. Toward this aim, we used in this study NHE1 null mutant mice and cDNA microarrays to investigate the effects of NHE1 on global gene expression in various regions of the brain, e.g., cortex, hippocampus, brain stem-diencephalon, and cerebellum. We found that a total of 35 to 79 genes were up- or downregulated in each brain region, with the majority being downregulated. The effect of NHE1 null mutation on gene expression is region specific, and only 11 genes were changed in all brain regions studied. Further analysis of the cis-regulatory regions of downregulated genes revealed that transcription suppressors, BCL6 and E4BP4, were probable candidates that mediated the inhibitory effect of NHE1 null mutation. One of the genes, MCT-13, was not only downregulated in the NHE1 null mutant brain but also in tissue cultures treated with an NHE1 inhibitor. We conclude that 1) a relatively small number of genes were altered in the NHE1 null mouse brain; 2) the effects of NHE1 null mutation on gene expression are region specific; and 3) several genes implicated in neurodegeneration have altered expression, potentially offering a molecular explanation for the phenotype of the NHE1 null mouse.

NHE1 null mutation; gene expression profile; microarray

This article has been cited by other articles:

				J. Xue, D. Zhou, H. Yao, and G. G. Haddad Role of transporters and ion channels in neuronal injury under hypoxia Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R451 - R457. [Abstract] [Full Text] [PDF]

				J. Xue, D. Zhou, H. Yao, O. Gavrialov, M. J. McConnell, B. D. Gelb, and G. G. Haddad Novel functional interaction between Na+/H+ exchanger 1 and tyrosine phosphatase SHP-2 Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2406 - R2416. [Abstract] [Full Text] [PDF]

				G. Li, D. Zhou, A. G. Vicencio, J. Ryu, J. Xue, A. Kanaan, O. Gavrialov, and G. G. Haddad Effect of carbon dioxide on neonatal mouse lung: a genomic approach J Appl Physiol, December 1, 2006; 101(6): 1556 - 1564. [Abstract] [Full Text] [PDF]

				J. Luo, H. Chen, D. B. Kintner, G. E. Shull, and D. Sun Decreased Neuronal Death in Na+/H+ Exchanger Isoform 1-Null Mice after In Vitro and In Vivo Ischemia J. Neurosci., December 7, 2005; 25(49): 11256 - 11268. [Abstract] [Full Text] [PDF]

				C. Fan, D. A. Iacobas, D. Zhou, Q. Chen, J. K. Lai, O. Gavrialov, and G. G. Haddad Gene expression and phenotypic characterization of mouse heart after chronic constant or intermittent hypoxia Physiol Genomics, August 11, 2005; 22(3): 292 - 307. [Abstract] [Full Text] [PDF]