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Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay.

ABSTRACT: 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.

SUBMITTER: Delaloy C

PROVIDER: S-EPMC1698764 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay.

Delaloy Céline C Hadchouel Juliette J Imbert-Teboul Martine M Clemessy Maud M Houot Anne-Marie AM Jeunemaitre Xavier X

The American journal of pathology 20060701 1

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 ...[more]

PMID: 16816365

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Dataset Information

Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay.

Publications

Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay.

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