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中国科学家培养“转基因”猴子用于自闭症研究

更新时间:2016-1-28 10:01:26 来源:纽约时报中文网 作者:佚名

Monkeys Built to Mimic Autism-Like Behaviors May Help Humans
中国科学家培养“转基因”猴子用于自闭症研究

Scientists have genetically engineered monkeys so that they exhibit behaviors similar to autism, with a goal of testing potential therapies on the animals in hopes that their resemblance to humans will yield more answers about the disorder.

科学家通过改造猴子的基因,让它们产生类似自闭症的行为,目标是在动物身上试验可能的疗法。科学家希望猴子与人类的相似性,可以帮助我们进一步解释这种心理障碍。

The scientists found that the monkeys showed “very similar behaviors related to human autism patients, including repetitive behaviors, increased anxiety and, most importantly, defects in social interactions,” said Zilong Qiu, a leader of the research at the Institute of Neuroscience at the Chinese Academy of Sciences in Shanghai. The team is now imaging the brains of the monkeys, he said, “trying to identify the deficiency in the brain circuits that is responsible for the autism-like behavior.”

科学家发现这些猴子表现出了“与人类自闭症患者十分相似的行为,包括重复刻板行为、焦虑行为加剧,以及最重要的一点,社交障碍,”研究团队的领导者仇子龙说。仇子龙是位于上海的中国科学院神经科学研究所的研究员。他说,研究团队目前正在扫描猴子的大脑,“我们试图找到引起类似自闭症行为的大脑回路中的缺陷。”

The research, published Monday in the journal Nature, appears to be the furthest along of several research efforts involving monkeys, usually marmosets or macaques, engineered with genes linked to autism.

该研究发表在了周一的《自然》(Nature)杂志上,在几项有关猴子的研究中似乎处于领先地位。此类研究常常改造狨属或猕猴有关自闭症的基因。

Much autism research has focused on mice because they are inexpensive and reproduce quickly. Though mice engineered with other genes have developed some autism-like behaviors, the complexity and variability of autism are difficult to study in those less-advanced animals.

很多自闭症的研究集中在小鼠上,因为小鼠价格便宜,繁殖迅速。尽管经过基因改造的小鼠也产生了类似自闭症的行为,但是这些进化程度较低的动物所表现出的自闭症的复杂度和多样性,很难用于研究。

“Mice are not in the same league when you’re talking about doing models of social cognition and interaction,” said Jonathan Sebat, chief of the Beyster Center of Psychiatric Genomics at the University of California San Diego, who was not involved in the monkey research. “They’re not even close.”

“谈到社交认知和互动模式时,小鼠和人类不在一个层次上,”乔纳森·赛巴特(Jonathan Sebat)说。赛巴特是加州大学圣迭戈分校(University of California San Diego)贝斯特精神疾病基因组学研究中心主任,他没有参与猴子的研究。“小鼠和人根本都算不上相近。”

Not only are mouse brains simpler than primate brains, but “mice reach maturity in a matter of months, and that doesn’t give you a lot of time to study their development,” Dr. Sebat said. “It’s very logical that a primate would make a better model of human development and neurodegeneration. It’s a no-brainer.”

小鼠不仅大脑不如灵长类动物复杂,而且“几个月就会成年,所以没有足够的时间来研究它们的发育情况。”赛巴特说,“灵长类动物更适合充当研究人类发育和神经退化的模型。这是显而易见的。”

Previously, American scientists have created monkeys with the mutation for Huntington’s disease.

此前,美国科学家曾通过基因变异让猴子患上亨廷顿病。

At the Institute of Neuroscience in China, other researchers are creating monkeys with genes linked to neuromotor and psychiatric disorders, said the director, Mu-Ming Poo.

在中科院神经科学研究所,其他研究者正在修改猴子与神经运动和精神障碍有关的基因,所长蒲慕明(Mu-Ming Poo)透露。

The overarching cause of autism is still unknown, and cases have been linked to about 100 mutations, some inherited and some developing spontaneously.

导致自闭症的主要原因尚未确定,研究发现自闭症病例与100种基因变异有关,其中一些可以遗传,一些则是自然发生。

The monkeys in the newly published research did not exhibit every aspect of autism or even every aspect of the genetic autism-like disorder the scientists were seeking to mirror. That disorder, MECP2 duplication syndrome, occurs when people, especially boys, inherit two copies of the MECP2 gene.

在新发表的研究中,猴子并没有出现自闭症的所有症状,甚至连科学家试图反映的一种类似遗传自闭症的障碍也并没有全部展现。它称为MECP2重复综合症,当人类,尤其是男孩,遗传两组MECP2基因时就会出现这种障碍。

The scientists used an inactive virus to inject the human MECP2 gene into eggs of female monkeys and then artificially inseminated the eggs and implanted the embryos into surrogate monkeys. They ended up with eight carrying the gene in the cortex and cerebellum of their brains.

科学家利用不活跃的病毒把人类的MECP2基因注入雌猴的卵子中,对该卵子进行人工授精,并将其植入胚胎中,以孕育猴子。最后,他们得到了八只大脑皮层和小脑中带有该基因的猴子。

The monkeys did not all have two copies of MECP2, as in the human syndrome, but most had more MECP2 than normal, an overexpression of the gene. The genetic change and the social deficits were also transmitted to a second generation of monkeys, Dr. Qiu said.

不是所有猴子都像患有该综合症的人类一样,带有两组MECP2基因,但是大多数猴子的MECP2基因比正常的猴子要多,这是基因的过表达。基因的改变和社交障碍也遗传给了下一代猴子,仇子龙说。

These monkeys were more likely than normal ones to run in circles in their cages, which the scientists considered an example of repetitive behavior. They showed more stress and defensive behavior, grunting more when people gazed at them, which the scientists said reflected autism-like anxiety. And they were less likely to be social by sitting with, touching or grooming other monkeys. As the monkeys got older, males showed more social disconnection, just as MECP2 syndrome is more common in boys, the researchers said.

和正常的猴子相比,这些猴子更倾向于在笼子里绕圈跑,科学家认为这是重复刻板行为的例子。这些猴子表现出了更多的紧张迹象,防卫行为更多,当人们盯着它们时,就会更多地发出哼哼的声音,科学家说,这些都是自闭症的焦虑症状。它们的社交倾向较低,与其他猴子坐在一起,抚摸其他猴子或给其他猴子梳毛的行为较少。猴子长大后,雄猴更容易与社会隔绝,这和MECP2综合症在男孩中更常见的情况一致,研究者表示。

But the monkeys also had significant limitations as models for MECP2 duplication syndrome and for autism in general, said Dr. Huda Zoghbi, professor of neuroscience and molecular and human genetics at Baylor College of Medicine.

但是作为MECP2重复综合症和更广泛的自闭症的实验模型,猴子仍然存在很大的局限性,贝勒医学院(Baylor College of Medicine)的神经学和分子人类遗传学教授胡达·佐格比博士(Huda Zoghbi)说。

Dr. Zoghbi, who helped discover that mutated forms of MECP2 cause Rett Syndrome, a type of autism that affects mostly girls, said the monkeys carried MECP2 only in neurons, not throughout the brain, as happens in humans. She questioned whether circling the cages was akin to repetitive behavior in autism and noted that the monkeys did not exhibit some crucial features of MECP2 duplication syndrome, like seizures and cognitive deficits.

佐格比参与了发现MECP2变异会引起雷特综合症(Rett Syndrome)的研究工作。这是一种主要在女孩中发生的自闭症类型。她表示,猴子携带的MECP2基因只存在于神经元中,而不是像人类一样遍布整个脑部。她质疑,在笼子里绕圈是否与自闭症中的重复刻板行为有关,并提出猴子并未出现MECP2重复综合症的一些关键特征,比如抽搐和认知缺陷。

Genetically engineering monkeys is much more costly and time-consuming than making transgenic mice, said Dr. Anthony Chan, whose research involves transgenic Huntington’s disease monkeys at Yerkes National Primate Research Center in Atlanta. Producing enough monkeys to test therapies takes years, he said, adding that an experiment like the Chinese one would cost “a few million dollars” and would be more expensive in the United States because of labor costs and less availability of monkeys, which are indigenous to China. Also, some animal rights advocates here are more troubled by research on monkeys than by research on rodents.

修改猴子的基因要比修改小鼠的基因成本更高,费时更多,安东尼·陈(Anthony Chan)博士说。他在亚特兰大的叶克斯国家灵长类研究中心(Yerkes National Primate Research Center)以猴子为基因实验体,研究亨廷顿病。他说,等猴子繁殖到足够的数量并试验疗法需要多年时间。他又补充道,像中国这样的试验,一次就要花费“数百万美元”,而在美国,那就更贵了,因为劳动力成本高,猴子的数量少。猴子在中国是土生土长的。另外,美国的动物权利倡导者更厌恶对猴子做实验,而不是啮齿类动物。

Still, some experts said that in some circumstances monkeys could help scientists better understand how autistic brains work and the effects of approaches like deep brain stimulation, gene therapy or medication. And monkeys, with longer life cycles than mice, may offer better opportunities to observe autism developing from infancy.

虽然如此,一些专家说在一些情况下,猴子能够帮助科学家更好地理解自闭症大脑的运作方式,以及大脑深度模拟、基因疗法或药物疗法的作用。因为猴子的生命周期长于小鼠,所以猴子从婴儿期就可以观察其自闭症的发展情况,为研究提供更多的机会。

Dr. Sebat at the University of California San Diego said that MECP2 duplication, which, while rare, is a common genetic cause of autism-like symptoms, “was a logical place to start in making a primate model of autism,” but that monkeys engineered with some other autism-linked genes would be better candidates for testing drugs.

加州大学圣迭戈分校的赛巴特说,MECP2重复虽然罕见,但它是导致自闭症类似症状的常见基因问题。“从这里开始建立自闭症的初步模型是顺理成章的”。但是修改猴子的其他一些与自闭症相关的基因可能会更有利于药物试验的进行。

Given the expense of engineering monkeys, experts said, mice should be made with various genes first, and “then a subset of these genetic models of autism in mouse can be studied much more intensely in primate models,” Dr. Sebat said. “The monkey is not going to replace the mouse.”

考虑到猴子基因工程的成本,专家说,应该先用小鼠进行多种基因的试验,“然后从小鼠的自闭症基因模式中选取一部分在灵长类模型中进行更深入的研究。”赛巴特说,“猴子是不会取代小鼠的。”

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