Retinal Pathology and Function in a Cln3 Knockout Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease)

• Published in: Molecular and cellular neuroscience 2002-04, Vol.19 (4), p.515-527
• Main Authors: Seigel, Gail M., Lotery, Andrew, Kummer, Ari, Bernard, David J., Greene, Nicholas D.E., Turmaine, Mark, Derksen, Todd, Nussbaum, Robert L., Davidson, Beverly, Wagner, Janet, Mitchison, Hannah M.
• Format: Article
• Language: English
• Subjects: Aging - genetics; Aging - metabolism; Animals; Apoptosis - genetics; Axons - metabolism; Axons - pathology; Axons - ultrastructure; Carbohydrate Metabolism; Carbohydrates - genetics; Disease Models, Animal; Female; Fluorescence; Fundus Oculi; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Inclusion Bodies - ultrastructure; Lectins; Male; Membrane Glycoproteins; Mice; Mice, Knockout; Molecular Chaperones; Mutation - genetics; Neuronal Ceroid-Lipofuscinoses - genetics; Neuronal Ceroid-Lipofuscinoses - metabolism; Neuronal Ceroid-Lipofuscinoses - pathology; Periodic Acid-Schiff Reaction; Photoreceptor Cells - metabolism; Photoreceptor Cells - pathology; Photoreceptor Cells - ultrastructure; Plant Lectins; Proteins - genetics; Proteins - metabolism; Retina - metabolism; Retina - pathology; Retina - ultrastructure; Retinal Diseases - genetics; Retinal Diseases - metabolism; Retinal Diseases - pathology; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Retinal Ganglion Cells - ultrastructure; Soybean Proteins
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1006/mcne.2001.1099

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.