title: Retinal pathology and function in a Cln3 knockout mouse model of juvenile Neuronal Ceroid Lipofuscinosis (batten disease).
abstract: Batten disease or JNCL, is the juvenile form of Neuronal Ceroid Lipofuscinosis (NCL) an autosomal recessive neurodegenerative disorder. Since retinal degeneration is an early consequence of Batten disease, we examined the eyes of Cln3 knockout mice (1-20 months of age), along with heterozygotes and appropriate controls, to determine whether or not the Cln3 defect would lead to characteristic retinal degeneration and visual loss. Accumulation of autofluorescent material and intracellular inclusions were markedly increased in Cln3 knockout retinal ganglion cells, as well as most other nuclear layers. Nerve fiber density was also significantly decreased in Cln3 knockout retinae. Apoptosis was observed in the photoreceptor layer of Cln3 knockout. However, the degree of retinal degeneration up to age 20 months was not extensive. Fundus examinations of Cln3 knockout mice showed no significant abnormalities, while electroretinograms remained robust through 11 months of age. In summary, it appears that accumulation of autofluorescent material, carbohydrate storage material, as well as apoptotic cell death are retinal manifestations of the Cln3 defect that do not appear to extinguish retinal function in this mouse model of Batten disease.
authors: Department of Ophthalmology, University of Rochester School of Medicine, New York, USA. gseigel@frontiernet.net
authors: Gail M
authors: GM
authors: Seigel
authors: Andrew
authors: A
authors: Lotery
authors: Ari
authors: A
authors: Kummer
authors: David J
authors: DJ
authors: Bernard
authors: Nicholas D E
authors: ND
authors: Greene
authors: Mark
authors: M
authors: Turmaine
authors: Todd
authors: T
authors: Derksen
authors: Robert L
authors: RL
authors: Nussbaum
authors: Beverly
authors: B
authors: Davidson
authors: Janet
authors: J
authors: Wagner
authors: Hannah M
authors: HM
authors: Mitchison
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D005654:Fundus Oculi; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D037102:Lectins; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009154:Mutation / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010503:Periodic Acid-Schiff Reaction; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D037121:Plant Lectins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012164:Retinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D030262:Soybean Proteins; D010835:Phytohemagglutinins
chemical_list: D002241:Carbohydrates; D037102:Lectins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D037121:Plant Lectins; D011506:Proteins; D030262:Soybean Proteins; C105199:CLN3 protein, human; C028824:soybean lectin; D010835:Phytohemagglutinins