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由于非人灵长类在生物学、遗传学和行为学等方面与人类的高度相似性，使之成为人类疾病理想的、甚至是不可替代的动物模型，在治疗、药理药效的临床前安全评价致关重要。转基因动物模型非常适合人类疾病的研究，特别是那些因遗传缺陷引起的疾病，转基因灵长类动物模型能很好表达人类疾病的变异基因，这种变异不会在转基因动物中存在个体差异，并能遗传致下一代。
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+ }6 t- M- k( _. X/ E由于生物学特性的差异，小动物模型，如啮齿类很难对人类疾病的治疗做出有效判断。例如，许多神经退行性疾病（如老年痴呆，帕金森氏病）已建立了啮齿类动物模型，但这些模型在脑内都未重现相关神经的损伤和丢失。然而，由于灵长类动物较长的生殖和生育周期，使灵长类转基因动物模型的建立较为困难。目前国际上仅有一例人类疾病的转基因猴报道，这项研究成果不仅是我国首例获得成功的转基因猕猴研究，同时也标志着昆明动物研究所在非人灵长类转基因动物研究方面达到了世界领先水平，这为未来人类重大疾病的非人灵长类动物模型的深入研究奠定了坚实的基础。10月12日，由中国科学院昆明动物研究所季维智研究员领导的研究小组关于非人灵长类转基因动物的研究于美国科学院院刊发表此项研究。（生物谷Bioon.com）5 ? E( U% ]+ u h' _1 W
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PNAS doi: 10.1073/pnas.1006563107
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Transgenic rhesus monkeys produced by gene transfer into early-cleavage–stage embryos using a simian immunodeficiency virus-based vector & z2 P: p2 }; z
Yuyu Niua,b,c,d,1, Yang Yue,1, Agnieszka Bernatf,g,h,1, Shihua Yanga,b,i, Xiechao Hea,b,c,d, Xiangyu Guoa,b,c,d, Dongliang Chena,b,c,d, Yongchang Chena,b,c,d, Shaohui Jia,b,c, Wei Sia,b,c,d, Yongqin Lva,b,c,d, Tao Tana,b,c,d, Qiang Weia,b,c,d, Hong Wanga,b,c,d, Lei Shia,b,c,d, Jean Guanj,k,l,m, Xuemei Zhul,m, Marielle Afanassieffe,f,g, Pierre Savatierf,g,h,2, Kang Zhangj,k,l,m,2, Qi Zhoue,2, and Weizhi Jia,b,c,d,2 & B6 f: t9 r/ q# Q9 w- p9 l
0 S" }, J. w0 p- r: a% G+ m* i, B* ^6 FaKunming Primate Research Center and
1 M' ^8 ^1 U- y2 tbKunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, People's Republic of China;
% J! Z: I- k, t* acKunming Biomed International and
& Y: k0 A) U2 @ u; V# _dNational Engineering Research Center of Biomedicine and Animal Science, Kunming 650051, People's Republic of China;
1 d% d% r4 V* Y% \+ N: ~) FeInstitute of Zoology, Chinese Academy of Sciences, Beijing 100860, People's Republic of China;
0 y* j# H8 r3 ]: `. `% wfInstitut National de la Santé et de la Recherche Médicale, U846, and
p* G; \ o+ FgPrimaStem Stem Cell and Brain Research Institute, Bron 69500, France;
* ~, d6 A+ j; Y4 O3 k: rhUniversité de Lyon, Lyon 69003, France; $ h- O6 [' H6 c9 E
iBiotechnology Research Center, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650093, People's Republic of China;
& \! {. m3 I9 \# d2 Q* ajCenter for Molecular Medicine and Department of Ophthalmology, West China Hospital and ; l2 t# e, P, O/ l0 o
kSichuan University, Chengdu 610065, People's Republic of China; and
6 l" T! J1 r% NlInstitute for Genomic Medicine and 0 N6 L) X; P0 |: U
mShiley Eye Center, University of California, San Diego, La Jolla, CA 92093 ! H- |# N: B, ]
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The development of transgenic technologies in monkeys is important for creating valuable animal models of human physiology so that the etiology of diseases can be studied and potential therapies for their amelioration may be developed. However, the efficiency of producing transgenic primate animals is presently very low, and there are few reports of success. We have developed an improved methodology for the production of transgenic rhesus monkeys, making use of a simian immunodeficiency virus (SIV)-based vector that encodes EGFP and a protocol for infection of early-cleavage–stage embryos. We show that infection does not alter embryo development. Moreover, the timing of infection, either before or during embryonic genome activation, has no observable effect on the level and stability of transgene expression. Of 70 embryos injected with concentrated virus at the one- to two-cell stage or the four- to eight-cell stage and showing fluorescence, 30 were transferred to surrogate mothers. One transgenic fetus was obtained from a fraternal triple pregnancy. Four infant monkeys were produced from four singleton pregnancies, of which two expressed EGFP throughout the whole body. These results demonstrate the usefulness of SIV-based lentiviral vectors for the generation of transgenic monkeys and improve the efficiency of transgenic technology in nonhuman primates. |
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发表于 2010-10-25 10:11
发表于 2010-11-15 21:36
