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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2008-11-21
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pubmed:abstractText |
Large deletions in intron 1 of the with-no-lysine kinase type 1 (WNK1) gene cause familial hyperkalemic hypertension. Alternative promoters generate functionally different isoforms: long ubiquitous isoforms (L-WNK1) and a kidney-specific isoform (KS-WNK1) lacking kinase activity. It remains unclear whether the disease-causing mutations selectively modify the synthesis of 1 or both types of isoforms. Using a transgenic mouse model, we found that intron 1 deletion resulted in the overexpression of L- and KS-WNK1 in the distal convoluted tubule and ubiquitous ectopic KS-WNK1 expression. Phylogenetic and functional analysis of the minimal 22-kb intron 1 deletion identified 1 repressor and 1 insulator, potentially preventing interactions between the regulatory elements of L-WNK1 and KS-WNK1. These results provide the first insight into the molecular mechanisms of WNK1-induced familial hyperkalemic hypertension.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1524-4563
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1149-54
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18955660-Animals,
pubmed-meshheading:18955660-Brain,
pubmed-meshheading:18955660-CHO Cells,
pubmed-meshheading:18955660-Cells, Cultured,
pubmed-meshheading:18955660-Cricetinae,
pubmed-meshheading:18955660-Cricetulus,
pubmed-meshheading:18955660-Disease Models, Animal,
pubmed-meshheading:18955660-Dogs,
pubmed-meshheading:18955660-Embryonic Stem Cells,
pubmed-meshheading:18955660-Female,
pubmed-meshheading:18955660-Gene Deletion,
pubmed-meshheading:18955660-Genes, Reporter,
pubmed-meshheading:18955660-Humans,
pubmed-meshheading:18955660-Hyperkalemia,
pubmed-meshheading:18955660-Hypertension, Renal,
pubmed-meshheading:18955660-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:18955660-Introns,
pubmed-meshheading:18955660-Kidney,
pubmed-meshheading:18955660-Leukocytes,
pubmed-meshheading:18955660-Male,
pubmed-meshheading:18955660-Mice,
pubmed-meshheading:18955660-Mice, Inbred C57BL,
pubmed-meshheading:18955660-Mice, Transgenic,
pubmed-meshheading:18955660-Muscle, Skeletal,
pubmed-meshheading:18955660-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18955660-Species Specificity
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pubmed:year |
2008
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pubmed:articleTitle |
Deletion of WNK1 first intron results in misregulation of both isoforms in renal and extrarenal tissues.
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pubmed:affiliation |
Faculté de Médecine, Université Paris Descartes Paris V, Collège de France, INSERM Unit 772, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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