Silencing of FUS in the common marmoset (Callithrix jacchus) brain via stereotaxic injection of an adeno-associated virus encoding shRNA

•The common marmoset FUS coding sequence was identified.•An AAV vector system for silencing FUS expression in the brain of the common marmoset was developed.•An immunological response provoked following FUS suppression was observed. Fused in sarcoma (FUS) is an RNA binding protein that is involved i...

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Bibliographic Details
Published in:Neuroscience research 2018-05, Vol.130, p.56-64
Main Authors: Endo, Kuniyuki, Ishigaki, Shinsuke, Masamizu, Yoshito, Fujioka, Yusuke, Watakabe, Akiya, Yamamori, Tetsuo, Hatanaka, Nobuhiko, Nambu, Atsushi, Okado, Haruo, Katsuno, Masahisa, Watanabe, Hirohisa, Matsuzaki, Masanori, Sobue, Gen
Format: Article
Language:English
Subjects:
Adenoviridae - physiology
Animals
Brain - metabolism
Callithrix
Common marmoset
Disease Models, Animal
Female
Frontotemporal lobar degeneration
Frontotemporal Lobar Degeneration - genetics
FUS
Genetic Vectors - administration & dosage
HEK293 Cells
Humans
Neurons - metabolism
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
RNA-Binding Protein FUS - antagonists & inhibitors
RNA-Binding Protein FUS - genetics
Stereotaxic Techniques
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Summary:•The common marmoset FUS coding sequence was identified.•An AAV vector system for silencing FUS expression in the brain of the common marmoset was developed.•An immunological response provoked following FUS suppression was observed. Fused in sarcoma (FUS) is an RNA binding protein that is involved in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). To establish the common marmoset (Callithrix jacchus) as a model for FTLD, we generated a stereotaxic injection-based marmoset model of FUS-silencing. We designed shRNAs against the marmoset FUS gene and generated an AAV9 virus encoding the most effective shRNA against FUS (shFUS). The AAV encoding shFUS (AAV-shFUS) was introduced into the frontal cortex of young adult marmosets, whereas AAV encoding a control shRNA was injected into the contralateral side. We obtained approximately 70–80% silencing of FUS following AAV-shFUS injection. Interestingly, FUS-silencing provoked a proliferation of astrocytes and microglias. Since FTLD is characterized by various emotional deficits, it would be helpful to establish a marmoset model of FUS-silencing in various brain tissues for investigating the pathomechanism of higher cognitive and behavioral dysfunction.
ISSN:0168-0102
1872-8111
DOI:10.1016/j.neures.2017.08.006