SIRT6 deficiency results in developmental retardation in cynomolgus monkeys

@article{Zhang2018SIRT6DR,
  title={SIRT6 deficiency results in developmental retardation in cynomolgus monkeys},
  author={Weiqi Zhang and Haifeng Wan and Gui-hai Feng and Jing Qu and Jiaqiang Wang and Yaobin Jing and Ruotong Ren and Zunpeng Liu and Linlin Zhang and Zhiguo Chen and Shuyan Wang and Yong Zhao and Zhaoxia Wang and Yun Yuan and Qi Zhou and Wei Li and Guanghui Liu and Baoyang Hu},
  journal={Nature},
  year={2018},
  volume={560},
  pages={661-665}
}
SIRT6 acts as a longevity protein in rodents1,2. However, its biological function in primates remains largely unknown. Here we generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model using a CRISPR–Cas9-based approach. SIRT6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19 (a developmental repressor), and we were able to recapitulate… 
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The results indicate that SIRT6 functions as a mediator of primate brain development by repressing the expression of H19 long non-coding RNA in a trans manner.
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It is demonstrated that the brain-specific deletion of Wt1 results in abnormal cell distribution during embryonic neurogenesis, which is accompanied by enhanced proliferation of neural progenitors and reduced neuronal differentiation, which could contribute to the understanding of MDD etiology and therapy.
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TLDR
It appears that during the brain organ evolution, Sirt6 has gained more relevance as the brain becomes bigger and more complex, observing the most detrimental effect in the brains of Homo sapiens.
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