Effect of targeted expression of clusterin in photoreceptor cells on retinal development and differentiation.
Clusterin expression is increased in tissues undergoing apoptosis, including neurodegenerative retina, but the causal relationships remain to be clarified. To test the hypothesis that overexpression of clusterin could induce apoptosis in neurons, transgenic mice were generated in which rat clusterin transgene was expressed in photoreceptor cells under the transcriptional control of the human interphotoreceptor retinoid-binding protein (IRBP) promoter. Photoreceptor cell death in the resulting transgenic mice was examined by histology and TUNEL techniques. The expression of the clusterin transgene was confirmed by in situ hybridization in the photoreceptor cells, and results in a complex pattern of clusterin protein distribution in the retina. A reduction in apoptotic staining in the transgenic retinas was observed from birth to postnatal day 15. These results suggest that clusterin is not causally involved in apoptotic mechanisms of photoreceptor cell death, but may relate to cytoprotective functions.
Jomary
C
C
British Retinitis Pigmentosa Society Laboratory, Department of Pharmacology, The Rayne Institute, GKT, St Thomas' Hospital, London SE1 7EH, UK. cjomary@hgmp.mrc.ac.uk
Chatelain
G
G
Michel
D
D
Weston
A
A
Neal
M J
MJ
Jones
S E
SE
D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D051152:Clusterin; D005136:Eye Proteins; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D010786:Photoreceptor Cells / Q000033:anatomy & histology / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000033:anatomy & histology / Q000254:growth & development*; D012177:Retinol-Binding Proteins / Q000235:genetics; D000099214:Retinol-Binding Proteins, Interstitial
D051152:Clusterin; D005136:Eye Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C495242:CLU protein, human; C495243:Clu protein, mouse