Event Details:
Hideyuki Okano
Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science
Department of Physiology, Keio University School of Medicine
Abstract
The common marmoset (Callithrix jacchus) is a small New World primate that has been extensively used as biomedical research models. There is also an increasing interest in common marmoset in Brain Science based on the its characteristic social behavior, human like trait and as a model for exploration and discovery of knowledge-based strategies for the eradication of major human brain disorders (Okano et al., Neuron, 2016; Grillner et al., Nat Neurosci, 2016) due to the availability of genetic modification (GM) technology. We first developed GM technology of marmoset by lentiviral mediated transgenesis (Sasaki et al., Nature, 2009), followed by generation of knock-out marmoset using genome editing (Sato et al., Cell Stem Cell, 2016). In the present talk, I wish to mention our recent data of generation of transgenic marmoset models of neurodegenerative diseases, including Parkinson disease (PD) which overexpressed the mutant form of a-synuclein suing lentiviral vector. The PD model marmoset showed stage-dependent progression of the disease, such as sleeping disturbance followed by motor deficit. In addition, I will mention a model marmoset of a neurodevelopmental disorder, the Rett syndrome, obtained by genome editing of MECP2 gene. Abnormalities in brain structure and function in these marmoset models may accelerate discovery of disease biomarkers and mechanisms toward translation (Okano et al., Neuron, 2016).
In the present talk, I will also introduce new methods so called “Quick Marmoset Projects” to generate neuroscience models (e.g. subsets of neurons-specific reporter-expressing marmosets, which enable us to explore neuronal activity at a single cell level in free moving marmosets (Kondo et al., Cell Reports, 2018) and disease models quickly through the in vivo genome editing in the post-natal marmoset brains, using homology-independent targeted integration (HITI) which can be applied for post-mitotic cells through the viral vector delivery to the brain by direct injection into brain parenchyma or across the blood-brain-barriers.