Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Neurobiology of disease, 2018-11, Vol.119, p.65-78

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. •We have discovered a novel CLN7−/− macaque model of Batten disease (BD).•Affected BD macaques bear a frameshift mutation in the CLN7 gene (CLN7−/−).•CLN7−/− macaques display progressive locomotor deficits including ataxia and tremor.•Brains from CLN7−/− macaques show accumulation of autofluorescent storage material.•Brains from CLN7−/− macaques show robust cerebral and cerebellar atrophy.