Phenotypic characterization of a mouse model of juvenile neuronal ceroid lipofuscinosis

NEUROBIOLOGY OF DISEASE

卷:29

Article

Katz, Martin L.^1,2  Johnson, Gary S.²  Tullis, Gregory E.³  Lei, Bo^1,4 

[1] Univ Missouri, Sch Med, Mason Eye Inst, Columbia, MO 65212 USA

[2] Univ Missouri, Dept Vet Pathol, Columbia, MO 65211 USA

[3] Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA

[4] Univ Missouri, Dept Vet Med & Surg, Columbia, MO 65211 USA

关键词: behavior;    neurodegeneration;    mouse model;    lysosomal storage;    retina;    brain;    batten disease;    electroretinogram;    CLN3;   

DOI  :  10.1016/j.nbd.2007.08.017

来源: Elsevier

【 摘 要 】

Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessively inherited neurodegenerative disorder that results from mutations in the CLN3 gene. JNCL is characterized by accumulation of autofluorescent lysosomal storage bodies, vision loss, seizures, progressive cognitive and motor decline, and premature death. Studies were undertaken to characterize the neuronal ceroid lipofuscinosis phenotype in a Cln3 knockout mouse model. Progressive accumulation of autofluorescent storage material was observed in brain and retina of affected mice. The Cln3(-/-) mice exhibited progressively impaired inner retinal function, altered pupillary light reflexes, losses of inner retinal neurons, and reduced brain mass. Behavioral changes included reduced spontaneous activity levels and impaired learning and memory. In addition, Cln3(-/-) mice had significantly shortened life spans. These phenotypic features indicate that the mouse model will be useful for investigating the mechanisms underlying the disease pathology in JNCL and provide quantitative markers of disease pathology that can be used for evaluating the efficacies of therapeutic interventions. (C) 2007 Elsevier Inc. All rights reserved.

【 授权许可】

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