| First Author | Delaloy C | Year | 2008 |
| Journal | Hypertension | Volume | 52 |
| Issue | 6 | Pages | 1149-54 |
| PubMed ID | 18955660 | Mgi Jnum | J:281501 |
| Mgi Id | MGI:6378868 | Doi | 10.1161/HYPERTENSIONAHA.108.120899 |
| Citation | Delaloy C, et al. (2008) Deletion of WNK1 first intron results in misregulation of both isoforms in renal and extrarenal tissues. Hypertension 52(6):1149-54 |
| 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. |
