PNAS：中国科学家培育出基因编辑瘦肉猪

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新华社华盛顿10月23日电(记者 林小春)中国科学家23日宣布,他们利用基因编辑方法培育出一批健康的瘦肉猪,比正常猪脂肪少24%.

    这项工作由中国科学院动物研究所赵建国领导完成,论文发表在新一期《PNAS，美国国家科学院学报》上.一些专家认为,这是一个重要进展.但也有人怀疑民众对基因编辑瘦肉猪的接受程度.

    赵建国研究团队通过新一代基因编辑工具CRISPR,向猪细胞内插入一种叫解偶联蛋白1(UCP1)的基因,减少脂肪沉积,增加瘦肉率,最终培育出的猪比正常猪脂肪少24%.

    赵建国对新华社记者说,"这为猪的新品种培育提供了良好的素材,也为通过基因编辑技术快速改良猪的数量性状提供了概念验证".

    他解释说,UCP1基因对维持动物的体温和能量平衡起重要作用.有研究表明,敲除UCP1能引起鼠变胖,而激活它则可以预防饮食引起的肥胖.但现代家猪的祖先在2000万年前就丢失了UCP1基因.

    为此,他们通过基因编辑工具将UCP1基因定点整合到猪胎儿的成纤维细胞的基因组中,培育出2500多个克隆猪胚胎,然后将这些胚胎注入13只代孕母猪体内,其中3只母猪怀孕并产下12只雄性仔猪.

    与野生型猪相比,这些仔猪体温调节能力显著增强,但脂肪率和膘厚度显著降低,瘦肉率显著提高.分析表明,UCP1基因主要通过促进脂肪水解来减少脂肪沉积,降低脂肪率.

    与此同时,UCP1基因并不影响猪的活动量,没有导致能量浪费.这些猪6月龄时被屠宰,屠体分析显示它们的体重和饲料转化率与野生型猪无异.此外,这12只雄性仔猪有一只与其他母猪交配,也成功生出了健康后代.

Significance

Uncoupling protein 1 (UCP1) is responsible for brown adipose tissue-mediated thermogenesis and plays a critical role in protecting against cold and regulating energy homeostasis. Modern pigs lack functional UCP1, which makes them susceptible to cold and prone to fat deposition and results in neonatal mortality and decreased production efficiency. In the current study, a CRISPR/Cas9-mediated homologous recombination-independent approach was established, and mouse adiponectin-UCP1 was efficiently inserted into the porcine endogenous UCP1 locus. The resultant UCP1 KI pigs showed an improved ability to maintain body temperature, decreased fat deposition, and increased carcass lean percentage. UCP1 KI pigs are a potentially valuable resource for the pig industry that can improve pig welfare and reduce economic losses.

Abstract

Uncoupling protein 1 (UCP1) is localized on the inner mitochondrial membrane and generates heat by uncoupling ATP synthesis from proton transit across the inner membrane. UCP1 is a key element of nonshivering thermogenesis and is most likely important in the regulation of body adiposity. Pigs (Artiodactyl family Suidae) lack a functional UCP1 gene, resulting in poor thermoregulation and susceptibility to cold, which is an economic and pig welfare issue owing to neonatal mortality. Pigs also have a tendency toward fat accumulation, which may be linked to their lack of UCP1, and thus influences the efficiency of pig production. Here, we report application of a CRISPR/Cas9-mediated, homologous recombination (HR)-independent approach to efficiently insert mouse adiponectin-UCP1 into the porcine endogenous UCP1 locus. The resultant UCP1 knock-in (KI) pigs showed an improved ability to maintain body temperature during acute cold exposure, but they did not have alterations in physical activity levels or total daily energy expenditure (DEE). Furthermore, ectopic UCP1 expression in white adipose tissue (WAT) dramatically decreased fat deposition by 4.89% (P < 0.01), consequently increasing carcass lean percentage (CLP; P < 0.05). Mechanism studies indicated that the loss of fat upon UCP1 activation in WAT was linked to elevated lipolysis. UCP1 KI pigs are a potentially valuable resource for agricultural production through their combination of cold adaptation, which improves pig welfare and reduces economic losses, with reduced fat deposition and increased lean meat production.

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