Cardiovascular expression of the mouse WNK1 gene during development and adulthood revealed by a BAC reporter assay.
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.
Delaloy
Céline
C
INSERM, Unit 772, Paris, France.
Hadchouel
Juliette
J
Imbert-Teboul
Martine
M
Clemessy
Maud
M
Houot
Anne-Marie
AM
Jeunemaitre
Xavier
X
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002531:Cerebellum / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D003331:Coronary Vessels / Q000196:embryology / Q000378:metabolism*; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D000076204:WNK Lysine-Deficient Protein Kinase 1
D007527:Isoenzymes; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse