Discovery of a CLN7 model of Batten disease in non-human primates

Jodi McBride, Martha Neuringer, Betsy Ferguson, Steven Kohama, Ian J. Tagge, Robert C. Zweig, Laurie M. Renner, Trevor McGill, Jonathan Stoddard, Samuel Peterson, Weiping Su, Lawrence (Larry) Sherman, Jacqueline S. Domire, Rebecca Ducore, Lois Colgin, Anne Lewis

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)65-78
Number of pages14
JournalNeurobiology of Disease
Volume119
DOIs
Publication statusPublished - Nov 1 2018

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Keywords

  • Batten disease
  • CLN7
  • Japanese macaque
  • Large animal model
  • Late infantile neuronal ceroid lipofuscinosis
  • Lysosomal storage disease
  • MFSD8
  • Neurodegeneration
  • Non-human primate
  • Retinal degeneration

ASJC Scopus subject areas

  • Neurology

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