Tetranectin Knockout Mice Develop Features of Parkinson Disease

Abstract

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.

Involvement of microRNA-135a-5p in the Protective Effects of Hydrogen Sulfide Against Parkinson's Disease

“…The precise etiology of Parkinson's disease remains unclear. The presently clinically used drug for treating Parkinson's disease is L-DOPA, which only ameliorates the symptoms but could not reverse the process of DA neuronal degeneration [6][7][8][9]. Therefore, development of effective therapeutic drugs for Parkinson's disease is in great need.…”

Tetranectin, a potential novel diagnostic biomarker of heart failure, is expressed within the myocardium and associates with cardiac fibrosis

“…Serum concentrations of Tetranectin decrease in pathological conditions such as cancer, inflammatory diseases, and coronary artery disease [9][10][11][12][13][14][15][16] . Tetranectin knockout (null) mice have shown to develop features consistent with Parkinson's disease when aged, and to have impaired fracture and wound healing processes; [17][18][19] however data from a cardiac phenotype in these mice is lacking.…”

Tetranectin as a Potential Biomarker for Stable Coronary Artery Disease

“…Of note, serum TN levels were independently associated with CAD, from the results of multivariable logistic regression analysis in the model including age, gender, BMI, smoking, hypertension, hyperlipidemia, diabetes mellitus, chronic obstructive pulmonary disease, serum glucose, liver function, BUN, Scr, UA, TG, TC, HDL-C, LDL-C and Lp(a) levels. According to TN’s structural and binding properties, we suspected that the underlying mechanism might be attributed to a high uptake by the formation of atherosclerotic plaques 22 23 , which are characterized by lipid, albumin, Lp(a) and fibrin/fibrinogen deposition 11 24 25 . Consistently, IHC results revealed high expression of TN in human atherosclerotic lesions.…”