title: 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: OBJECTIVE
  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.affiliation: IRO, Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: Joane
authors.initials: J
authors.lastname: Le Carré
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: Sandra
authors.initials: S
authors.lastname: Cottet
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002829:Choroid / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D005136:Eye Proteins / Q000235:genetics*; D015870:Gene Expression; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D057130:Leber Congenital Amaurosis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012172:Retinaldehyde / Q000172:deficiency; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D006026:Glycoside Hydrolases; D012313:RNA; D012333:RNA, Messenger; D012172:Retinaldehyde; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C561288:Glb1l3 protein, mouse