TY - JOUR
T1 - Silencing of FUS in the common marmoset (Callithrix jacchus) brain via stereotaxic injection of an adeno-associated virus encoding shRNA
AU - Endo, Kuniyuki
AU - Ishigaki, Shinsuke
AU - Masamizu, Yoshito
AU - Fujioka, Yusuke
AU - Watakabe, Akiya
AU - Yamamori, Tetsuo
AU - Hatanaka, Nobuhiko
AU - Nambu, Atsushi
AU - Okado, Haruo
AU - Katsuno, Masahisa
AU - Watanabe, Hirohisa
AU - Matsuzaki, Masanori
AU - Sobue, Gen
N1 - Funding Information:
This study represents the results of Brain/MINDS of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and the Japan Agency for Medical Research and Development (AMED). A part of this study represents the results of the “Integrated Research on Depression, Dementia and Development Disorders” and the “Construction of System for Spread of Primate Model Animals” projects carried out under the Strategic Research Program for Brain Sciences by AMED. It was also supported by Grant-in-Aid for Scientific Research on Innovative Areas, “Brain Protein Aging and Dementia control” and “Non-linear Neuro-oscillology” from MEXT.
Publisher Copyright:
© 2017 Elsevier Ireland Ltd and Japan Neuroscience Society
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neures.2017.08.006
DO - 10.1016/j.neures.2017.08.006
M3 - Article
C2 - 28842245
AN - SCOPUS:85028604320
VL - 130
SP - 56
EP - 64
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
ER -