Retinal pathology and function in a Cln3 knockout mouse model of juvenile Neuronal Ceroid Lipofuscinosis (batten disease).
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.
Seigel
Gail M
GM
Department of Ophthalmology, University of Rochester School of Medicine, New York, USA. gseigel@frontiernet.net
Lotery
Andrew
A
Kummer
Ari
A
Bernard
David J
DJ
Greene
Nicholas D E
ND
Turmaine
Mark
M
Derksen
Todd
T
Nussbaum
Robert L
RL
Davidson
Beverly
B
Wagner
Janet
J
Mitchison
Hannah M
HM
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
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