Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure.

Human molecular genetics | Oct 15, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19633012

We recently generated Wnk4(D561A/+) knockin mice and found that a major pathogenesis of pseudohypoaldosteronism type II was the activation of the OSR1/SPAK kinase-NaCl cotransporter (NCC) phosphorylation cascade by the mutant WNK4. However, the physiological roles of wild-type WNK4 on the regulation of Na excretion and blood pressure, and whether wild-type WNK4 functions positively or negatively in this cascade, remained to be determined. In the present study, we generated WNK4 hypomorphic mice by deleting exon 7 of the Wnk4 gene. These mice did not show hypokalemia and metabolic alkalosis, but they did exhibit low blood pressure and increased Na and K excretion under low-salt diet. Phosphorylation of OSR1/SPAK and NCC was significantly reduced in the mutant mice as compared with their wild-type littermates. Protein levels of ROMK and Maxi K were not changed, but epithelial Na channel appeared to be activated as a compensatory mechanism for the reduced NCC function. Thus, wild-type WNK4 is a positive regulator for the WNK-OSR1/SPAK-NCC cascade, and WNK4 is a potential target of anti-hypertensive drugs.

Pubmed ID: 19633012 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Biological Transport | Blood Pressure | Disease Models, Animal | Female | Gene Silencing | Male | Mice | Mice, Inbred C57BL | Molecular Sequence Data | Phosphorylation | Potassium | Protein-Serine-Threonine Kinases | Pseudohypoaldosteronism | Receptors, Drug | Sodium | Solute Carrier Family 12, Member 3 | Symporters

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.