Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells.
OBJECTIVE
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.
Lenzner
Steffen
S
Max Planck Institute for Molecular Genetics, Berlin, Germany. lenzner@molgen.mpg.de
Prietz
Sandra
S
Feil
Silke
S
Nuber
Ulrike A
UA
Ropers
H-Hilger
HH
Berger
Wolfgang
W
D000818:Animals; D001766:Blindness / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000032:analysis; D003638:Deafness / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005136:Eye Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008607:Intellectual Disability / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D012163:Retinal Detachment / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D014960:X Chromosome / Q000235:genetics*
D018076:DNA, Complementary; D005136:Eye Proteins; C489916:Ndph protein, mouse; D009419:Nerve Tissue Proteins