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 this process in a human neural progenitor cell differentiation system. SIRT6 deficiency results in histone hyperacetylation at the imprinting control region of H19, CTCF recruitment and upregulation of H19. Our results suggest that SIRT6 is involved in regulating development in non-human primates, and may provide mechanistic insight into human perinatal lethality syndrome.A cynomolgus monkey model deficient in SIRT6 protein exhibits severe retardation in prenatal development, in which neuronal differentiation is delayed by activation of the H19 long non-coding RNA.

中文翻译：

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SIRT6 缺乏导致食蟹猴发育迟缓

SIRT6 在啮齿动物中充当长寿蛋白 1,2。然而，它在灵长类动物中的生物学功能仍然未知。在这里，我们使用基于 CRISPR–Cas9 的方法生成了一个 SIRT6-null 食蟹猴 (Macaca fascicularis) 模型。SIRT6 缺陷的猴子在出生后数小时死亡，并表现出严重的产前发育迟缓。SIRT6 缺失通过转录激活长链非编码 RNA H19（一种发育抑制因子）来延迟神经元分化，我们能够在人类神经祖细胞分化系统中重现这一过程。SIRT6 缺乏导致 H19 印记控制区的组蛋白过度乙酰化、CTCF 募集和 H19 的上调。我们的结果表明 SIRT6 参与调节非人类灵长类动物的发育，