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(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*{dagger}{ddagger}, Juliette Hadchouel*{dagger}, Martine Imbert-Teboul§, Maud Clemessy*{dagger}, Anne-Marie Houot*{dagger} and Xavier Jeunemaitre*{dagger}

From INSERM,* Unit 772, Paris; the Collège de France,{dagger} Paris; the Université Paris 6,{ddagger} 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.




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