Linked Life Data

12191971

Source:http://linkedlifedata.com/resource/pubmed/id/12191971

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-8-22
pubmed:abstractText
Mutations in the Aquaporin-2 gene, which encodes a renal water channel, have been shown to cause autosomal nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. Most AQP2 missense mutants in recessive NDI are retained in the endoplasmic reticulum (ER), but AQP2-T125M and AQP2-G175R were reported to be nonfunctional channels unimpaired in their routing to the plasma membrane. In five families, seven novel AQP2 gene mutations were identified and their cell-biologic basis for causing recessive NDI was analyzed. The patients in four families were homozygous for mutations, encoding AQP2-L28P, AQP2-A47V, AQP2-V71M, or AQP2-P185A. Expression in oocytes revealed that all these mutants, and also AQP2-T125M and AQP2-G175R, conferred a reduced water permeability compared with wt-AQP2, which was due to ER retardation. The patient in the fifth family had a G>A nucleotide substitution in the splice donor site of one allele that results in an out-of-frame protein. The other allele has a nucleotide deletion (c652delC) and a missense mutation (V194I). The routing and function of AQP2-V194I in oocytes was not different from wt-AQP2; it was therefore concluded that c652delC, which leads to an out-of-frame protein, is the NDI-causing mutation of the second allele. This study indicates that misfolding and ER retention is the main, and possibly only, cell-biologic basis for recessive NDI caused by missense AQP2 proteins. In addition, the reduced single channel water permeability of AQP2-A47V (40%) and AQP2-T125M (25%) might become of therapeutic value when chemical chaperones can be found that restore their routing to the plasma membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2267-77
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12191971-Amino Acid Sequence, pubmed-meshheading:12191971-Animals, pubmed-meshheading:12191971-Aquaporin 2, pubmed-meshheading:12191971-Aquaporin 6, pubmed-meshheading:12191971-Aquaporins, pubmed-meshheading:12191971-Cell Line, pubmed-meshheading:12191971-Cell Membrane, pubmed-meshheading:12191971-Diabetes Insipidus, Nephrogenic, pubmed-meshheading:12191971-Family Health, pubmed-meshheading:12191971-Female, pubmed-meshheading:12191971-Genes, Recessive, pubmed-meshheading:12191971-Humans, pubmed-meshheading:12191971-Infant, Newborn, pubmed-meshheading:12191971-Male, pubmed-meshheading:12191971-Molecular Sequence Data, pubmed-meshheading:12191971-Mutation, Missense, pubmed-meshheading:12191971-Oocytes, pubmed-meshheading:12191971-Pedigree, pubmed-meshheading:12191971-Protein Structure, Tertiary, pubmed-meshheading:12191971-Protein Transport, pubmed-meshheading:12191971-Water, pubmed-meshheading:12191971-Xenopus
pubmed:year
2002
pubmed:articleTitle
Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus.
pubmed:affiliation
Department of Cell Physiology, UMC St. Radboud, Nijmegen, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't