Tetranectin knockout mice develop features of Parkinson disease.
نویسندگان
چکیده
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.
منابع مشابه
H2-EB1 Molecule Alleviates Allergic Rhinitis Symptoms of H2-Eb1 Knockout Mice
Background: H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis. Objective: To establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in H2-Eb1 knockout mice as a model of AR. Methods: The Cre/Lox...
متن کاملA potential role for tetranectin in mineralization during osteogenesis
Tetranectin is a protein shared by the blood and the extracellular matrix. Tetranectin is composed of four identical, noncovalently bound polypeptides each with a molecular mass of approximately 21 kD. There is some evidence that tetranectin may be involved in fibrinolysis and proteolysis during tissue remodeling, but its precise biological function is not known. Tetranectin is enriched in the ...
متن کاملEffects of capsaicin in low doses and high doses on the small intestine motor response in wild-type and TRPV1 knockout mice
متن کامل
Generation of global Spata19 knockout mouse using CRISPR/Cas9 nickase technology
Introduction: SPATA19 gene is expressed in developmental stages of testis and some organs, but so far its function has only been examined in the testis. In this study, we provided an effective pathway for the generation of these mice using new CRISPR / Cas9 nickase method while generating Spata19 knockout mice for future studies in other organs. Materials and Methods: CRISPR / Cas9 nickase plas...
متن کاملIntegrin α1/Akita double knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy
Animal models that mimic human diabetic nephropathy are useful to identify key factors in pathogenesis of this disease, as well as the development of new therapies. Several mouse models of diabetes have features of human diabetic nephropathy, yet none of these completely fulfill the Animal Models of Diabetes Complications Consortium criteria and completely reproduce pathological and functional ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
دوره 34 2 شماره
صفحات -
تاریخ انتشار 2014