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

Mol Vis. 2011:17:1287-97. Epub 2011 May 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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