Molecular Neurobiology

, Volume 54, Issue 3, pp 1745–1758 | Cite as

Transduction Profile of the Marmoset Central Nervous System Using Adeno-Associated Virus Serotype 9 Vectors

  • Yasunori Matsuzaki
  • Ayumu Konno
  • Ryo Mukai
  • Fumiaki Honda
  • Masafumi Hirato
  • Yuhei Yoshimoto
  • Hirokazu Hirai
Article

Abstract

The common marmoset is a small New World primate that has attracted remarkable attention as a potential experimental animal link between rodents and humans. Adeno-associated virus (AAV) vector-mediated expression of a disease-causing gene or a potential therapeutic gene in the brain may allow the construction of a marmoset model of a brain disorder or an exploration of the possibility of gene therapy. To gain more insights into AAV vector-mediated transduction profiles in the marmoset central nervous system (CNS), we delivered AAV serotype 9 (AAV9) vectors expressing GFP to the cisterna magna or the cerebellar cortex. Intracisternally injected AAV9 vectors expanded in the CNS according to the cerebrospinal fluid (CSF) flow, by retrograde transport through neuronal axons or via intermediary transcytosis, resulting in diffuse and global transduction within the CNS. In contrast, cerebellar parenchymal injection intensely transduced a more limited area, including the cerebellar cortex and cerebellar afferents, such as neurons of the pontine nuclei, vestibular nucleus and inferior olivary nucleus. In the spinal cord, both administration routes resulted in labeling of the dorsal column and spinocerebellar tracts, presumably by retrograde transport from the medulla oblongata and cerebellum, respectively. Motor neurons and dorsal root ganglia were also transduced, possibly by diffusion of the vector down the subarachnoid space along the cord. Thus, these two administration routes led to distinct transduction patterns in the marmoset CNS, which could be utilized to generate different disease animal models and to deliver therapeutic genes for the treatment of diseases affecting distinct brain areas.

Keywords

Common marmoset Adeno-associated virus serotype 9 vector Stereology Cerebellum Spinal cord Gene transfer 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yasunori Matsuzaki
    • 1
  • Ayumu Konno
    • 1
  • Ryo Mukai
    • 2
  • Fumiaki Honda
    • 3
  • Masafumi Hirato
    • 3
  • Yuhei Yoshimoto
    • 3
  • Hirokazu Hirai
    • 1
  1. 1.Department of Neurophysiology and Neural RepairGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of OphthalmologyGunma University Graduate School of MedicineMaebashiJapan
  3. 3.Department of NeurosurgeryGunma University Graduate School of MedicineMaebashiJapan

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