Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome Yang SS; Lo YF; Yu IS; Lin SW; Chang TH; Hsu YJ; Chao TK; Sytwu HK; Uchida S; Sasaki S; Lin SHHum Mutat 2010[Dec]; 31 (12): 1304-15Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypomagnesemia, hypokalemic metabolic alkalosis, and hypocalciuria. To better model human GS caused by a specific mutation in the thiazide-sensitive Na(+) -Cl(-) cotransporter (NCC) gene SLC12A3, we generated a nonsense Ncc Ser707X knockin mouse corresponding to human p.Ser710X (c.2135C>A), a recurrent mutation with severe phenotypes in Chinese GS patients. Compared with wild-type or heterozygous littermates, homozygous (Hom) knockin mice fully recapitulated the phenotype of human GS. The markedly reduced Ncc mRNA and virtually absent Ncc protein expression in kidneys of Hom mice was primarily due to nonsense-mediated mRNA decay (NMD) surveillance mechanisms. Expression of epithelial Na(+) channel (Enac), Ca(2+) channels (Trpv5 and Trpv6), and K(+) channels (Romk1 and maxi-K) were significantly increased. Late distal convoluted tubules (DCT) volume was increased and DCT cell ultrastructure appeared intact. High K(+) intake could not correct hypokalemia but caused a further increase in maxi-K but not Romk1 expression. Renal tissue from a patient with GS also showed the enhanced TRPV5 and ROMK1 expression in distal tubules. We suggest that the upregulation of TRPV5/6 and of ROMK1 and Maxi-K may contribute to hypocalciuria and hypokalemia in Ncc Ser707X knockin mice and human GS, respectively.|*Disease Models, Animal[MESH]|Animals[MESH]|Base Sequence[MESH]|Calcium Channels/metabolism[MESH]|Cell Size/drug effects[MESH]|Codon, Nonsense/genetics[MESH]|Diet[MESH]|Female[MESH]|Fluorescent Antibody Technique[MESH]|Gene Knock-In Techniques/*methods[MESH]|Gitelman Syndrome/*genetics/pathology[MESH]|Humans[MESH]|Kidney/drug effects/metabolism/pathology/ultrastructure[MESH]|Male[MESH]|Mice[MESH]|Middle Aged[MESH]|Molecular Sequence Data[MESH]|Phenotype[MESH]|Potassium Chloride/administration & dosage/pharmacology[MESH]|RNA Stability/drug effects/genetics[MESH]|Receptors, Drug/*genetics/metabolism[MESH]|Serine/*genetics[MESH]|Sodium/metabolism[MESH]|Solute Carrier Family 12, Member 3[MESH]|Symporters/*genetics/metabolism[MESH]|Thiazides/*pharmacology[MESH]|Young Adult[MESH] |
