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Molecular, Biochemical, and Genetic Techniques

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Cerebellar transduction profiles after ssAAV9 injection via cortical, intrathecal or intravenous routes

  • P2-382
  • Fathul Huda:1,2 Ayumu Konno:1 Yasunori Matsuzaki:1 Hanna Goenawan:1,2 Koichi Miyake:3 Takashi Shimada:3 Hirokazu Hirai:1 
  • 1:Department of Neurophysiology, Gunma University Graduate School of Medicine 2:Department of Physiology, Faculty of Medicine Universitas Padjadjaran 3:Department of Biochemistry and Molecular Biology, Nippon Medical School 

Using single-stranded adeno-associated virus serotype 9 (ssAAV9) vectors containing the neuron-specific synapsin-I promoter, we examined whether different administration routes (direct cerebellar cortical (DC), intrathecal (IT) and intravenous (IV) injections) could elicit specific transduction profiles in the CNS. The DC injection route robustly and exclusively transduced the whole cerebellum, whereas the IT injection route primarily transduced the cerebellar lobules 9 and 10 close to the injection site and the spinal cord. An IV injection in neonatal mice weakly and homogenously transduced broad CNS areas. In the cerebellar cortex, the DC and IT injection routes transduced all neuron types, whereas the IV injection route primarily transduced Purkinje cells We then made AAV9 construct containing ATXN1 transgene to produce a mouse model of spinocerebellar ataxia type 1 (SCA1). We observed intranuclear aggregation of mutant ATXN1 in Purkinje cells, significant atrophy of the Purkinje cell dendrites and progressive motor deficits, which are characteristics of SCA1. Thus, ssAAV9-mediated transduction areas, levels and cell types change depending on the route of injection. Moreover, this approach can be used for the generation of different mouse models of CNS/neurodegenerative diseases.

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