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

Am J Pathol. 2006 Jul;169(1):105-18. doi: 10.2353/ajpath.2006.051290.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Cerebellum / metabolism
  • Chromosomes, Artificial, Bacterial*
  • Coronary Vessels / embryology
  • Coronary Vessels / metabolism*
  • Genes, Reporter*
  • Heart / embryology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kidney / metabolism
  • Mice
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Protein Serine-Threonine Kinases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transgenes
  • WNK Lysine-Deficient Protein Kinase 1

Substances

  • Isoenzymes
  • Minor Histocompatibility Antigens
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • Wnk1 protein, mouse