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Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells

Lenzner, Steffen; Prietz, Sandra; Feil, Silke; Nuber, Ulrike LU ; Ropers, H-Hilger and Berger, Wolfgang (2002) In Investigative Ophthalmology & Visual Science 43(9). p.2825-2833
Abstract
PURPOSE: Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP). The gene product is a cystine-knot-containing extracellular signaling molecule of unknown function. In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level. METHODS: Gene transcription in the eyes of 2-year-old Ndp knockout mice was compared with that in the eyes of age-matched wild-type control animals, by means of cDNA subtraction and microarrays. Clones (n = 3072) from the cDNA subtraction libraries were spotted... (More)
PURPOSE: Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP). The gene product is a cystine-knot-containing extracellular signaling molecule of unknown function. In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level. METHODS: Gene transcription in the eyes of 2-year-old Ndp knockout mice was compared with that in the eyes of age-matched wild-type control animals, by means of cDNA subtraction and microarrays. Clones (n = 3072) from the cDNA subtraction libraries were spotted onto glass slides and hybridized with fluorescently labeled RNA-derived targets. More than 230 differentially expressed clones were sequenced, and their expression patterns were verified by virtual Northern blot analysis. RESULTS: Numerous gene transcripts that are absent or downregulated in the eye of Ndp knockout mice are photoreceptor cell specific. In younger Ndp knockout mice (up to 1 year old), however, all these transcripts were found to be expressed at normal levels. CONCLUSIONS: The identification of numerous photoreceptor cell-specific transcripts with a reduced expression in 2-year-old, but not in young, Ndp knockout mice indicates that normal gene expression in these light-sensitive cells of mutant mice is established and maintained over a long period and that rods and cones are affected relatively late in the mouse model of ND. Obviously, the absence of the Ndp gene product is not compatible with long-term survival of photoreceptor cells in the mouse. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Investigative Ophthalmology & Visual Science
volume
43
issue
9
pages
2825 - 2833
publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
external identifiers
  • pmid:12202498
  • scopus:0036725825
ISSN
1552-5783
language
English
LU publication?
no
id
96e4cf36-8da2-4daa-be66-ce040cde2858 (old id 1125398)
alternative location
http://www.iovs.org/cgi/content/abstract/43/9/2825
date added to LUP
2008-05-26 14:37:53
date last changed
2017-11-12 03:54:03
@article{96e4cf36-8da2-4daa-be66-ce040cde2858,
  abstract     = {PURPOSE: Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP). The gene product is a cystine-knot-containing extracellular signaling molecule of unknown function. In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level. METHODS: Gene transcription in the eyes of 2-year-old Ndp knockout mice was compared with that in the eyes of age-matched wild-type control animals, by means of cDNA subtraction and microarrays. Clones (n = 3072) from the cDNA subtraction libraries were spotted onto glass slides and hybridized with fluorescently labeled RNA-derived targets. More than 230 differentially expressed clones were sequenced, and their expression patterns were verified by virtual Northern blot analysis. RESULTS: Numerous gene transcripts that are absent or downregulated in the eye of Ndp knockout mice are photoreceptor cell specific. In younger Ndp knockout mice (up to 1 year old), however, all these transcripts were found to be expressed at normal levels. CONCLUSIONS: The identification of numerous photoreceptor cell-specific transcripts with a reduced expression in 2-year-old, but not in young, Ndp knockout mice indicates that normal gene expression in these light-sensitive cells of mutant mice is established and maintained over a long period and that rods and cones are affected relatively late in the mouse model of ND. Obviously, the absence of the Ndp gene product is not compatible with long-term survival of photoreceptor cells in the mouse.},
  author       = {Lenzner, Steffen and Prietz, Sandra and Feil, Silke and Nuber, Ulrike and Ropers, H-Hilger and Berger, Wolfgang},
  issn         = {1552-5783},
  language     = {eng},
  number       = {9},
  pages        = {2825--2833},
  publisher    = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
  series       = {Investigative Ophthalmology & Visual Science},
  title        = {Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells},
  volume       = {43},
  year         = {2002},
}