@article{0e8e938be7e4437aa3b90e1c287a379e,
title = "Discovery of a CLN7 model of Batten disease in non-human primates",
abstract = "We have identified a natural Japanese macaque model of the childhood neurodegenerative disorder neuronal ceroid lipofuscinosis, commonly known as Batten Disease, caused by a homozygous frameshift mutation in the CLN7 gene (CLN7−/−). Affected macaques display progressive neurological deficits including visual impairment, tremor, incoordination, ataxia and impaired balance. Imaging, functional and pathological studies revealed that CLN7−/− macaques have reduced retinal thickness and retinal function early in disease, followed by profound cerebral and cerebellar atrophy that progresses over a five to six-year disease course. Histological analyses showed an accumulation of cerebral, cerebellar and cardiac storage material as well as degeneration of neurons, white matter fragmentation and reactive gliosis throughout the brain of affected animals. This novel CLN7−/− macaque model recapitulates key behavioral and neuropathological features of human Batten Disease and provides novel insights into the pathophysiology linked to CLN7 mutations. These animals will be invaluable for evaluating promising therapeutic strategies for this devastating disease.",
keywords = "Batten disease, CLN7, Japanese macaque, Large animal model, Late infantile neuronal ceroid lipofuscinosis, Lysosomal storage disease, MFSD8, Neurodegeneration, Non-human primate, Retinal degeneration",
author = "McBride, {Jodi L.} and Martha Neuringer and Betsy Ferguson and Steven Kohama and Tagge, {Ian J.} and Zweig, {Robert C.} and Renner, {Laurie M.} and McGill, {Trevor J.} and Jonathan Stoddard and Samuel Peterson and Weiping Su and Sherman, {Larry S.} and Domire, {Jacqueline S.} and Rebecca Ducore and Colgin, {Lois M.} and Lewis, {Anne D.}",
note = "Funding Information: We thank the Division of Comparative Medicine (DCM) at the ONPRC for the maintenance of the Japanese Macaque Breeding Colony and for their outstanding veterinary care of the animals, with special acknowledgement to Gregory Timmel, DVM (Chief of DCM), Lauren Drew Martin, DVM (Assistant Chief of DCM) and Brandy Dozier, DVM (lead veterinarian for the Division of Neuroscience at the ONPRC). We kindly thank Melissa Williams in the OHSU Multiscale Microscopy Core for her assistance with the electron microscopy analysis. We also thank Dr. Nathan Selden MD, PhD, FACS, FAAP at OHSU for the thoughtful discussions and input concerning the identification of the BD macaque model as well as ongoing and future therapeutic strategies. This work made use of DNAs obtained from the ONPRC NHP DNA Bank, was supported by the ONPRC Japanese Macaque Resource, and funded by NIH Grants P51OD011092, NS10416 and P30 EY010572 , as well as unrestricted departmental funding from Research to Prevent Blindness (New York, NY). Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = nov,
doi = "10.1016/j.nbd.2018.07.013",
language = "English (US)",
volume = "119",
pages = "65--78",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
}