title: Degeneration of Photoreceptor Cells in Arylsulfatase G-Deficient Mice.
abstract: OBJECTIVE
  Retinal degeneration is a common feature of several lysosomal storage disorders, including the mucopolysaccharidoses, a group of metabolic disorders that is characterized by widespread accumulation of glycosaminoglycans due to lysosomal enzyme dysfunction. We used a new mouse model of mucopolysaccharidosis IIIE to study the effect of Arylsulfatase G (ARSG) deficiency on retina integrity.
  
  
  METHODS
  The retina of Arsg knockout mice aged 1 to 24 months was studied by immunohistochemistry and Western blot analysis. Electron microscopic analyses were performed on retinas from 15- and 22-month-old animals. Photoreceptor and microglia cell numbers and retina thickness were determined to quantitatively characterize retinal degeneration in ARSG-deficient mice.
  
  
  RESULTS
  Arsg knockout mice showed a progressive degeneration of photoreceptor cells starting between 1 and 6 months of age, resulting in the loss of more than 50% of photoreceptor cells in 24-month-old mice. Photoreceptor loss was accompanied by reactive astrogliosis, reactive microgliosis that was evident in the outer but not inner retina, and elevated expression levels of some lysosomal proteins. Electron microscopic analyses of retinas revealed no evidence for the presence of storage vacuoles. Of note, expression of ARSG protein in wild-type mice was detectable only in the RPE which, however, appeared morphologically unaffected in knockout mice at the electron microscopic level.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study demonstrating that ARSG deficiency results in progressive photoreceptor degeneration and dysregulation of various lysosomal proteins.
authors.affiliation: Department of Ophthalmology University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kruszewski
authors.affiliation: Anatomical Institute, University of Kiel, Kiel, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Lüllmann-Rauch
authors.affiliation: Biochemistry I, Department of Chemistry, Bielefeld University, Bielefeld, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dierks
authors.affiliation: Department of Ophthalmology University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Bartsch
authors.affiliation: Department of Biochemistry, University of Kiel, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Damme
mesh_terms: D000818:Animals; D001192:Arylsulfatases / Q000172:deficiency* / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D009084:Mucopolysaccharidosis III / Q000175:diagnosis / Q000201:enzymology*; D010786:Photoreceptor Cells / Q000201:enzymology* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D012162:Retinal Degeneration / Q000175:diagnosis / Q000201:enzymology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D011506:Proteins; C018589:lysosomal proteins; C000593694:arylsulfatase G, mouse; D001192:Arylsulfatases; D001619:beta-N-Acetylhexosaminidases