scholarly journals Generation and analysis of knock-in mice carrying pseudohypoaldosteronism type II-causing mutations in the cullin 3 gene

Biology Open ◽  
2015 ◽  
Vol 4 (11) ◽  
pp. 1509-1517 ◽  
Author(s):  
Y. Araki ◽  
T. Rai ◽  
E. Sohara ◽  
T. Mori ◽  
Y. Inoue ◽  
...  
Keyword(s):  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

scholarly journals Revisiting the NaCl cotransporter regulation by with-no-lysine kinases

2015 ◽  
Vol 308 (10) ◽  
pp. C779-C791 ◽  
Author(s):  
Silvana Bazúa-Valenti ◽  
Gerardo Gamba
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Type Ii ◽  
Complex Issue ◽  
Dark Ages ◽  
Ubiquitin Ligase Complex ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Increased Activity ◽  
Pseudohypoaldosteronism Type

The renal thiazide-sensitive Na+-Cl− cotransporter (NCC) is the salt transporter in the distal convoluted tubule. Its activity is fundamental for defining blood pressure levels. Decreased NCC activity is associated with salt-remediable arterial hypotension with hypokalemia (Gitelman disease), while increased activity results in salt-sensitive arterial hypertension with hyperkalemia (pseudohypoaldosteronism type II; PHAII). The discovery of four different genes causing PHAII revealed a complex multiprotein system that regulates the activity of NCC. Two genes encode for with-no-lysine (K) kinases WNK1 and WNK4, while two encode for kelch-like 3 (KLHL3) and cullin 3 (CUL3) proteins that form a RING type E3 ubiquitin ligase complex. Extensive research has shown that WNK1 and WNK4 are the targets for the KLHL3-CUL3 complex and that WNKs modulate the activity of NCC by means of intermediary Ste20-type kinases known as SPAK or OSR1. The understanding of the effect of WNKs on NCC is a complex issue, but recent evidence discussed in this review suggests that we could be reaching the end of the dark ages regarding this matter.

scholarly journals A novel mutation in exon 9 of Cullin 3 gene contributes to aberrant splicing in pseudohypoaldosteronism type II

FEBS Open Bio ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 461-469 ◽  
Author(s):  
Leping Shao ◽  
Li Cui ◽  
Jingru Lu ◽  
Yanhua Lang ◽  
Irene Bottillo ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Type Ii ◽  
Aberrant Splicing ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Exon 9 ◽  
Pseudohypoaldosteronism Type

scholarly journals A young child with pseudohypoaldosteronism type II by a mutation of Cullin 3

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Shoji Tsuji ◽  
Miyoko Yamashita ◽  
Gen Unishi ◽  
Reiko Takewa ◽  
Takahisa Kimata ◽  
...  
Keyword(s):  
Young Child ◽  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

Familial cases of pseudohypoaldosteronism type II harboring a novel mutation in the Cullin 3 gene

Nephrology ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 818-821
Author(s):  
Kiyoshi Nakano ◽  
Yasuo Kubota ◽  
Takayuki Mori ◽  
Motoko Chiga ◽  
Takayasu Mori ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Type Ii ◽  
Familial Cases ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

Decreased KLHL3 expression is involved in the pathogenesis of pseudohypoaldosteronism type II caused by cullin 3 mutation in vivo

2018 ◽  
Vol 22 (6) ◽  
pp. 1251-1257 ◽  
Author(s):  
Sayaka Yoshida ◽  
Yuya Araki ◽  
Takayasu Mori ◽  
Emi Sasaki ◽  
Yuri Kasagi ◽  
...  
Keyword(s):  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Cullin 3 ◽  
Pseudohypoaldosteronism Type

scholarly journals A New Locus on Chromosome 12p13.3 for Pseudohypoaldosteronism Type II, an Autosomal Dominant Form of Hypertension

2000 ◽  
Vol 67 (2) ◽  
pp. 302-310 ◽  
Author(s):  
Sandra Disse-Nicodème ◽  
Jean-Michel Achard ◽  
Isabelle Desitter ◽  
Anne-Marie Houot ◽  
Albert Fournier ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Type Ii ◽  
Dominant Form ◽  
Pseudohypoaldosteronism Type Ii ◽  
Autosomal Dominant Form ◽  
Pseudohypoaldosteronism Type

CUL3 gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy

2013 ◽  
Vol 28 (9) ◽  
pp. 1881-1884 ◽  
Author(s):  
Madori Osawa ◽  
Yumi Ogura ◽  
Kiyoshi Isobe ◽  
Shinichi Uchida ◽  
Shigeaki Nonoyama ◽  
...  
Keyword(s):  
Early Intervention ◽  
Gene Analysis ◽  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Pseudohypoaldosteronism Type

Pseudohypoaldosteronism Type II

2009 ◽  
pp. 1744-1745
Author(s):  
Markus Braun-Falco ◽  
Henry J. Mankin ◽  
Sharon L. Wenger ◽  
Markus Braun-Falco ◽  
Stephan DiSean Kendall ◽  
...  
Keyword(s):  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Pseudohypoaldosteronism Type

A mouse model of pseudohypoaldosteronism type II reveals a novel mechanism of renal tubular acidosis

2018 ◽  
Vol 94 (3) ◽  
pp. 514-523 ◽  
Author(s):  
Karen I. López-Cayuqueo ◽  
Maria Chavez-Canales ◽  
Alexia Pillot ◽  
Pascal Houillier ◽  
Maximilien Jayat ◽  
...  
Keyword(s):  
Mouse Model ◽  
Renal Tubular Acidosis ◽  
Type Ii ◽  
Pseudohypoaldosteronism Type Ii ◽  
Renal Tubular ◽  
Pseudohypoaldosteronism Type

scholarly journals KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3

2017 ◽  
Vol 37 (7) ◽  
Author(s):  
Emi Sasaki ◽  
Koichiro Susa ◽  
Takayasu Mori ◽  
Kiyoshi Isobe ◽  
Yuya Araki ◽  
...  
Keyword(s):  
Physiological Role ◽  
Hereditary Disease ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Type Ii ◽  
Dominant Type ◽  
Pseudohypoaldosteronism Type Ii ◽  
Negative Effect ◽  
Pseudohypoaldosteronism Type

ABSTRACT Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from the defective degradation of WNK1 and WNK4 by the KLHL3/CUL3 ubiquitin ligase complex. However, the other physiological in vivo roles of KLHL3 remain unclear. Therefore, here we generated KLHL3 −/− mice that expressed β-galactosidase (β-Gal) under the control of the endogenous KLHL3 promoter. Immunoblots of β-Gal and LacZ staining revealed that KLHL3 was expressed in some organs, such as brain. However, the expression levels of WNK kinases were not increased in any of these organs other than the kidney, where WNK1 and WNK4 increased in KLHL3−/− mice but not in KLHL3+/− mice. KLHL3−/− mice also showed PHAII-like phenotypes, whereas KLHL3+/− mice did not. This clearly demonstrates that the heterozygous deletion of KLHL3 was not sufficient to cause PHAII, indicating that autosomal dominant type PHAII is caused by the dominant negative effect of mutant KLHL3. We further demonstrated that the dimerization of KLHL3 can explain this dominant negative effect. These findings could help us to further understand the physiological roles of KLHL3 and the pathophysiology of PHAII caused by mutant KLHL3.

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