Influence of different promoters on the expression pattern of mutated human alpha-synuclein in transgenic mice.

نویسندگان

  • Lyutha Maskri
  • XinRan Zhu
  • Sabrina Fritzen
  • Kati Kühn
  • Christoph Ullmer
  • Peter Engels
  • Michael Andriske
  • Christine C Stichel
  • Hermann Lübbert
چکیده

Two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (asyn) are associated with rare, dominantly inherited forms of Parkinson's disease (PD) and its accumulation in Lewy bodies and Lewy neurites. As an initial step in investigating the role of asyn in the pathogenesis of PD, we have generated C57BL/6 transgenic mice overexpressing the doubly mutated human asyn under the control of three different promoters; the chicken beta-actin (chbetaactin), the mouse tyrosine hydroxylase 9.6 kb (msTH) and the mouse prion protein (msprp). In this study we compared the regional and cellular expression pattern of the transgenic protein in the brain and peripheral organs of various transgenic mouse lines. Western blot analysis and immunohistochemistry consistently showed that all three promoters successfully drive the expression of the transgene. The msprp promoter was found to give the highest level of transgene expression. All promoters directed the expression into the brain and specific neuron types. However, the promoters differed with respect to (i) the expression pattern in peripheral organs, (ii) the number and (iii) the regional distribution of expressing cells in the brain. Furthermore, remarkable line-to-line variation of expression patterns was observed in mouse lines carrying the same construct. Future studies will analyze how the variations in transgene expression affect the pathogenesis in the animals.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Alpha-synuclein induced apoptosis and proliferation interacted with CD44 in human lymphocytes

Human ?-synuclein is a 140 amino acid protein with little or no secondary structure. The ?-synuclein is expressed at high levels in the brain and enriched in neural synaptic terminals but its physiological function remains largely unknown. More recently, ?-synuclein has been shown to be one of the principal componets of Lewy bodies, neuronal inclusions that are found in diverse human neurodegen...

متن کامل

Alpha-synuclein induced apoptosis and proliferation interacted with CD44 in human lymphocytes

Human ?-synuclein is a 140 amino acid protein with little or no secondary structure. The ?-synuclein is expressed at high levels in the brain and enriched in neural synaptic terminals but its physiological function remains largely unknown. More recently, ?-synuclein has been shown to be one of the principal componets of Lewy bodies, neuronal inclusions that are found in diverse human neurodegen...

متن کامل

Tissue Specific Expression of Human Calcitonin Gene in Potato Tubers by an Organ Specific Promoter

To increase the production level of heterologous proteins in plants, strategies such as choice of strongerpromoters, optimization of codon usage and specific localization of foreign proteins are of major concern.Calcitonin (CT), a 32 amino acid polypeptide is a powerful and specific inhibitor of bone resorption and isused to treat several human diseases. Calcitonin activity is...

متن کامل

Genetic mouse models for Parkinson's disease display severe pathology in glial cell mitochondria.

We recently described mitochondrial pathology in neurons of transgenic mice with genes associated with Parkinson's disease (PD). Now we describe severe mitochondrial damage in glial cells of the mesencephalon in mice carrying a targeted deletion of parkin (PaKO) or overexpressing doubly mutated human alpha-synuclein (asyn). The number of mitochondria with altered morphology in glial cells is ce...

متن کامل

Clioquinol-induced ordered conformational behavior in alpha-synuclein: promising relevance for therapeutic approach to Parkinson's disease

Parkinson?¦s disease (PD) is a devastating and an intricate complex neurological disorder that results from the progressive degeneration of nerve cells in Substantia nigra that controls movement. The pathological hallmark of PD is the formation of insoluble protein aggregates known as lewey bodies. Alpha-synuclein is the major constituent of these fibrillar structures. Alpha-synuclein a 140 ami...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Neuro-degenerative diseases

دوره 1 6  شماره 

صفحات  -

تاریخ انتشار 2004