A platform for studies of Huntington’s disease on the basis of induced pluripotent stem cells

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Abstract

Huntington’s disease (HD) is one of the most severe hereditary neurodegenerative disorders caused by CAG repeats expansion in the HTT gene. A recently elaborated technology of genetic reprogramming allows obtaining induced pluripotent stem (iPS) cells from fibroblasts and other differentiated somatic cells. These iPS cells can grow in culture and differentiate in any cell types, including neurons, necessary for studies of molecular mechanisms of HD and other neurodegenerative diseases. We obtained, with the use of lentivirus transfection, iPS cells from primary fibroblasts biopsied from three female patients with HD (42–46 copies of the CAG repeats in the mutant allele). The efficiency of reprogramming was approximately 0.2%. The embryoid bodies were obtained from some clones of iPS cells, and derivatives of all the three embryo layers were shown to be formed as a result of spontaneous iPC cells differentiation. At present, our cell lines represent a unique platform for studies of HD. It may be used for establishing an effective system aimed at discoveries of molecular mechanisms undelaying HD and high-throughput search for novel neuroprotective drugs.

 

About the authors

E. D. Nekrasov

N.I .Vavilov Institute of General Genetics, Russian Academy of Sciences

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

O. S. Lebedeva

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

E. M. Vasina

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

A. N. Bogomazova

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

I. V. Chestkov

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

S. L. Kiselev

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

M. A. Lagarkova

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

S. A. Klyushnikov

Research Center of Neurology, Russian Academy of Medical Sciences (Moscow)

Email: platonova@neurology.ru
Russian Federation

S. N. Illarioshkin

Research Center of Neurology, Russian Academy of Medical Sciences (Moscow)

Email: platonova@neurology.ru
Russian Federation

I. A. Grivennikov

Institute of Molecular Genetics, Russian Academy of Sciences

Email: platonova@neurology.ru
Russian Federation

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Copyright (c) 2012 Nekrasov E.D., Lebedeva O.S., Vasina E.M., Bogomazova A.N., Chestkov I.V., Kiselev S.L., Lagarkova M.A., Klyushnikov S.A., Illarioshkin S.N., Grivennikov I.A.

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