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.

Abstract

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.

• Authors: Joane Le Carré, Daniel F Schorderet, Sandra Cottet
• Journal: Molecular vision (Mol Vis) Vol. 17 Pg. 1287-97 ( 2011) ISSN: 1090-0535 [Electronic] United States
• PMID: 21633714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Molecular Vision

Chemical References

• Carrier Proteins
• Eye Proteins
• Glb1l3 protein, mouse
• RNA, Messenger
• RNA
• retinoid isomerohydrolase
• Glycoside Hydrolases
• cis-trans-Isomerases
• Retinaldehyde

Topics

• Aging (metabolism)
• Animals
• Animals, Newborn (growth & development, metabolism)
• Carrier Proteins (genetics)
• Choroid (metabolism)
• Disease Models, Animal
• Disease Progression
• Down-Regulation
• Eye Proteins (genetics)
• Gene Expression
• Glycoside Hydrolases (genetics, metabolism)
• Immunohistochemistry
• In Situ Hybridization
• Leber Congenital Amaurosis (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout (genetics)
• RNA (metabolism)
• RNA, Messenger (metabolism)
• Retinal Degeneration (genetics, metabolism)
• Retinal Pigment Epithelium (metabolism)
• Retinaldehyde (deficiency)
• cis-trans-Isomerases