Linked Life Data

15254014

Source:http://linkedlifedata.com/resource/pubmed/id/15254014

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2004-8-26
pubmed:abstractText
Peripherin/rds (P/rds) is a membrane glycoprotein essential for the photoreceptor outer segment disc morphogenesis and maintenance. More than half of the disease-causing mutations in P/rds have been linked to different forms of macular dystrophy; the most common one is substitution of tryptophan for arginine at position 172 (R172W). Here we confirm the patient phenotype associated with the expression of R172W mutation in transgenic mice. Functional, structural and biochemical analyses showed that, while R172W P/rds is appropriately localized, a direct correlation exists between transgene expression levels and the onset/severity of the phenotype. In the wild-type background, both cone and rod photoreceptors' structure and function were significantly diminished, which indicates a dominant-negative, cone-rod defect. Whereas rds(+/-) mice maintained the normal cone function at early ages, cone responses in R172W/rds(+/-) mice were diminished to 41% of the wild-type level signifying a preferential damaging effect of the mutation on cones. Conversely, R172W/rds(+/-) mice showed a significant rescue of rod function and improvement of rod outer segment structure. Although rds(-/-) mice have no detectable rod or cone responses, R172W/rds(-/-) animals retained 30% of wild-type structure and rod function, but no significant rescue of cone function was detected at 1 month of age. No biochemical abnormalities were observed in complex formation and association with Rom-1; however, R172W protein was more sensitive to tryptic digestion, indicative of a change in protein conformation, possibly contributing to the cone-dominated phenotype. As the first animal model for P/rds-associated cone-rod dystrophy, R172W mice provide a valuable tool for studying the pathophysiology of P/rds-associated human retinal dystrophies and the development of therapeutic strategies to intervene in these diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2075-87
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15254014-Animals, pubmed-meshheading:15254014-Dark Adaptation, pubmed-meshheading:15254014-Eye Proteins, pubmed-meshheading:15254014-Intermediate Filament Proteins, pubmed-meshheading:15254014-Membrane Glycoproteins, pubmed-meshheading:15254014-Membrane Proteins, pubmed-meshheading:15254014-Mice, pubmed-meshheading:15254014-Mice, Transgenic, pubmed-meshheading:15254014-Nerve Tissue Proteins, pubmed-meshheading:15254014-Photoreceptor Cells, Vertebrate, pubmed-meshheading:15254014-Point Mutation, pubmed-meshheading:15254014-Protein Conformation, pubmed-meshheading:15254014-Retina, pubmed-meshheading:15254014-Retinal Cone Photoreceptor Cells, pubmed-meshheading:15254014-Retinal Degeneration, pubmed-meshheading:15254014-Retinal Rod Photoreceptor Cells, pubmed-meshheading:15254014-Rod Cell Outer Segment, pubmed-meshheading:15254014-Tetraspanins
pubmed:year
2004
pubmed:articleTitle
The R172W mutation in peripherin/rds causes a cone-rod dystrophy in transgenic mice.
pubmed:affiliation
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't