title: Retinal function in aging homozygous Cln3 (Δex7/8) knock-in mice.
abstract: Neuronal ceroid lipofuscinoses (NCL) are characterized by lysosomal accumulation of autofluorescent material and lead to degeneration of the central nervous system. Patients affected by the juvenile form of NCL (JNCL), the most common form of the disease, develop visual failure prior to mental and motor deficits. It is currently unclear if the corresponding mouse model, Cln3 (Δex7/8) knock-in, develops the same retinal phenotype and electroretinogram (ERG) measurements as affected patients. The aim of our study was to investigate the visual disease progression in the Cln3 (Δex7/8) mice using scotopic and photopic ERGs as well as optokinetic tracking (OKT) at different ages. The results were then compared with age-matched controls.The amplitudes of the a-wave and b-wave (scotopic ERG) decrease significantly in Cln3 (Δex7/8) mice starting at the age of 12 months. A reduction in the b/a-amplitude ratio indicates a degeneration preferentially of the inner retina. An amplitude reduction observed in the Cln3 (+/+) control mice may be attributed to an additional Crb1 (rd8) mutation. Using optokinetic tracking (OKT) the Cln3 (Δex7/8) mice show a progressive decline in visual acuity after 12 months of age.
authors.affiliation: Department of Ophthalmology, University Eye Clinic Regensburg, Franz-Josef-Strauß Allee 11, 93053, Regensburg, Germany, volz@eye-regensburg.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Volz
authors.forename: Myriam
authors.initials: M
authors.lastname: Mirza
authors.forename: Thomas
authors.initials: T
authors.lastname: Langmann
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D055253:Color Vision / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D055879:Gene Knock-In Techniques; D006720:Homozygote; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones / Q000235:genetics* / Q000502:physiology*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000503:physiopathology*; D055254:Night Vision / Q000502:physiology; D012160:Retina / Q000503:physiopathology*
chemical_list: C102229:CLN3 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones