title: Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons.
abstract: Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessive disorder of childhood caused by mutations in CLN3. Although visual deterioration is typically the first clinical sign to manifest in affected children, loss of Cln3 in a mouse model of JNCL does not recapitulate this retinal deterioration. This suggests that either the loss of CLN3 does not directly affect retinal cell survival or that nuclei involved in visual processing are affected prior to retinal degeneration. Having previously demonstrated that Cln3(-/-) mice have decreased optic nerve axonal density, we now demonstrate a decrease in nerve conduction. Examination of retino-recipient regions revealed a decreased number of neurons within the dorsal lateral geniculate nucleus (LGNd). We demonstrate decreased transport of amino acids from the retina to the LGN, suggesting an impediment in communication between the retina and projection nuclei. This study defines a novel path of degeneration within the LGNd, providing a mechanism for causation of JNCL visual deficits.
authors.affiliation: Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Weimer
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Custer
authors.forename: Jared W
authors.initials: JW
authors.lastname: Benedict
authors.forename: Noreen A
authors.initials: NA
authors.lastname: Alexander
authors.forename: Evan
authors.initials: E
authors.lastname: Kingsley
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005829:Geniculate Bodies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009901:Optic Nerve Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015354:Vision, Low / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: C102229:CLN3 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones