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Transgenic Rhesus Monkeys Carrying the Human MCPH1 Gene Copies show Human-like Neoteny of Brain Development
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Shi, L ; Luo, X ; Jiang, J ; Chen, YC; Liu, CR ; Hu, T ;Li, M ; Lin, Q ;Li, YJ ;Huang, J ;Wang, H ; Niu, YY ;Shi, YD ;Styner, M ;Wang, JH;Lu, Y ;Sun, XJ;Yu, HL; Ji, WZ;Su, B |
Abstract: |
Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive. Here, we successfully generated 11 transgenic rhesus monkeys (8 first-generation and 3 second-generation) carrying human copies of MCPH1, an important gene for brain development and brain evolution. Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation, resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys, similar to the known evolutionary change of developmental delay (neoteny) in humans. Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes, providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys. More importantly, the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task. The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits
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2019 |
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152453 |
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National Science Review |
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https://academic.oup.com/nsr/article-pdf/6/3/480/28834155/nwz043.pdf |
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