Tetranectin Knockout Mice Develop Features of Parkinson Disease

Cellular Physiology and Biochemistry

关键词: Tetranectin;    Parkinson disease;    Motor deficits;    α-synuclein;    Lewy bodies;   

DOI  :  10.1159/000362998

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Aggregation of insoluble α-synuclein to form Lewy bodies (LBs) may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD). Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN) gene (TN^-/-) and measured the behavioral and histopathological features of PD. Results Aged (15-to 20-month-old) TN^-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia) and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc) and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT) mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion The TN^-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

【 授权许可】

CC BY-NC-ND