Tetranectin Knockout Mice Develop Features of Parkinson Disease
- Resource Type
- Authors
- Xiao-ping Zhang; Yi-rui Sun; Wen-wei Gao; Er-song Wang; Yao-dong Ji; Hui-bin Yao; Gan Wang; Shiwen Chen; Hai-jun Yao; Caihua Xi
- Source
- Cellular Physiology and Biochemistry, Vol 34, Iss 2, Pp 277-287 (2014)
- Subject
- medicine.medical_specialty
Pathology
Physiology
α-synuclein
Substantia nigra
Striatum
Biology
Motor deficits
Neuroprotection
Polymerase Chain Reaction
lcsh:Physiology
lcsh:Biochemistry
Mice
Dopamine
Internal medicine
medicine
Animals
Lectins, C-Type
lcsh:QD415-436
DNA Primers
Synucleinopathies
Mice, Knockout
Base Sequence
lcsh:QP1-981
Pars compacta
Tetranectin
Dopaminergic
Parkinson disease
Disease Models, Animal
Endocrinology
nervous system
Knockout mouse
alpha-Synuclein
Lewy bodies
medicine.drug
- Language
- English
- ISSN
- 1421-9778
1015-8987
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.