This Article Full Text Full Text (PDF) Supplemental Material Supplemental Material Purchase Article View Shopping Cart Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Delaloy, C. Articles by Jeunemaitre, X. Search for Related Content PubMed PubMed Citation Articles by Delaloy, C. Articles by Jeunemaitre, X.

(American Journal of Pathology. 2006;169:105-118.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051290

Cardiovascular Expression of the Mouse WNK1 Gene during Development and Adulthood Revealed by a BAC Reporter Assay

Céline Delaloy^*, Juliette Hadchouel^*, Martine Imbert-Teboul, Maud Clemessy^*, Anne-Marie Houot^* and Xavier Jeunemaitre^*¶

From INSERM,^* Unit 772, Paris; the Collège de France, Paris; the Université Paris 6, Pierre et Marie Curie, Paris; CNRS, UMR 7134, Paris; and Faculté de Médecine,^¶ Université René Descartes, Paris, France

Large deletions in WNK1 are associated with inherited arterial hypertension. WNK1 encodes two types of protein: a kidney-specific isoform (KS-WNK1) lacking kinase activity and a ubiquitously expressed full-length isoform (L-WNK1) with serine threonine kinase activity. Disease is thought to result from hypermorphic mutations increasing the production of one or both isoforms. However, the pattern of L-WNK1 expression remains poorly characterized. We generated transgenic mice bearing a murine WNK1 BAC containing the nlacZ reporter gene for monitoring L-WNK1 expression during development and adulthood. We observed previously unsuspected early expression in the vessels and primitive heart during embryogenesis, consistent with the early death of WNK1^–/– mice. The generalized cardiovascular expression observed in adulthood may also suggest a possible kidney-independent role in blood pressure regulation. The second unsuspected site of L-WNK1 expression was the granular layer and Purkinje cells of the cerebellum, suggesting a role in local ion balance or cell trafficking. In the kidney, discordance between endogenous L-WNK1 and transgene expression suggests that either cis-regulatory elements important for physiological renal expression lie outside the BAC sequence or that illegitimate interactions occur between promoters. Despite this limitation, this transgenic model is a potentially valuable tool for the analysis of spatial and temporal aspects of WNK1 expression and regulation.

This article has been cited by other articles:

				Z. Zhang, X. Xu, Y. Zhang, J. Zhou, Z. Yu, and C. He LINGO-1 Interacts with WNK1 to Regulate Nogo-induced Inhibition of Neurite Extension J. Biol. Chem., June 5, 2009; 284(23): 15717 - 15728. [Abstract] [Full Text] [PDF]

				M. A. Ikram, S. Seshadri, J. C. Bis, M. Fornage, A. L. DeStefano, Y. S. Aulchenko, S. Debette, T. Lumley, A. R. Folsom, E. G. van den Herik, et al. Genomewide Association Studies of Stroke N. Engl. J. Med., April 23, 2009; 360(17): 1718 - 1728. [Abstract] [Full Text] [PDF]

				C. Delaloy, E. Elvira-Matelot, M. Clemessy, X.-o. Zhou, M. Imbert-Teboul, A.-M. Houot, X. Jeunemaitre, and J. Hadchouel Deletion of WNK1 First Intron Results in Misregulation of Both Isoforms in Renal and Extrarenal Tissues Hypertension, December 1, 2008; 52(6): 1149 - 1154. [Abstract] [Full Text] [PDF]

				J. A. McCormick, C.-L. Yang, and D. H. Ellison WNK Kinases and Renal Sodium Transport in Health and Disease: An Integrated View Hypertension, March 1, 2008; 51(3): 588 - 596. [Full Text] [PDF]