Altered expression of β-galactosidase-1-like protein 3 (Glb1l3) in the retinal pigment epithelium (RPE)-specific 65-kDa protein knock-out mouse model of Leber’s congenital amaurosis
| Autor: | Le Carré, J., Schorderet, D.F., Cottet, S. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
cis-trans-Isomerases
Aging Glycoside Hydrolases Leber Congenital Amaurosis Down-Regulation Gene Expression Retinal Pigment Epithelium Mice Animals RNA Messenger Eye Proteins In Situ Hybridization Mice Knockout Choroid Retinal Degeneration Immunohistochemistry eye diseases Mice Inbred C57BL Disease Models Animal Animals Newborn Disease Progression Retinaldehyde RNA sense organs Carrier Proteins Research Article |
| Zdroj: | Molecular Vision Molecular Vision, vol. 17, pp. 1287-1297 |
| ISSN: | 1090-0535 |
| Popis: | Purpose In this study, we investigated the expression of the gene encoding β-galactosidase (Glb)-1-like protein 3 (Glb1l3), a member of the glycosyl hydrolase 35 family, during retinal degeneration in the retinal pigment epithelium (RPE)-specific 65-kDa protein knockout (Rpe65−/−) mouse model of Leber congenital amaurosis (LCA). Additionally, we assessed the expression of the other members of this protein family, including β-galactosidase-1 (Glb1), β-galactosidase-1-like (Glb1l), and β-galactosidase-1-like protein 2 (Glb1l2). Methods The structural features of Glb1l3 were assessed using bioinformatic tools. mRNA expression of Glb-related genes was investigated by oligonucleotide microarray, real-time PCR, and reverse transcription (RT) -PCR. The localized expression of Glb1l3 was assessed by combined in situ hybridization and immunohistochemistry. Results Glb1l3 was the only Glb-related member strongly downregulated in Rpe65−/− retinas before the onset and during progression of the disease. Glb1l3 mRNA was only expressed in the retinal layers and the RPE/choroid. The other Glb-related genes were ubiquitously expressed in different ocular tissues, including the cornea and lens. In the healthy retina, expression of Glb1l3 was strongly induced during postnatal retinal development; age-related increased expression persisted during adulthood and aging. Conclusions These data highlight early-onset downregulation of Glb1l3 in Rpe65-related disease. They further indicate that impaired expression of Glb1l3 is mostly due to the absence of the chromophore 11-cis retinal, suggesting that Rpe65 deficiency may have many metabolic consequences in the underlying neuroretina. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|