由于非人靈長類在生物學,、遺傳學和行為學等方面與人類的高度相似性,，使之成為人類疾病理想的、甚至是不可替代的動物模型,，在治療,、藥理藥效的臨床前安全評價致關重要。轉基因動物模型非常適合人類疾病的研究,，特別是那些因遺傳缺陷引起的疾病,，轉基因靈長類動物模型能很好表達人類疾病的變異基因，這種變異不會在轉基因動物中存在個體差異,，并能遺傳致下一代,。
由于生物學特性的差異,，小動物模型，如嚙齒類很難對人類疾病的治療做出有效判斷,。例如,，許多神經退行性疾病（如老年癡呆,，帕金森氏?。┮呀⒘藝X類動物模型，但這些模型在腦內都未重現(xiàn)相關神經的損傷和丟失,。然而,，由于靈長類動物較長的生殖和生育周期，使靈長類轉基因動物模型的建立較為困難,。目前國際上僅有一例人類疾病的轉基因猴報道,，這項研究成果不僅是我國首例獲得成功的轉基因獼猴研究，同時也標志著昆明動物研究所在非人靈長類轉基因動物研究方面達到了世界領先水平,，這為未來人類重大疾病的非人靈長類動物模型的深入研究奠定了堅實的基礎,。10月12日，由中國科學院昆明動物研究所季維智研究員領導的研究小組關于非人靈長類轉基因動物的研究于美國科學院院刊發(fā)表此項研究,。（生物谷Bioon.com）
生物谷推薦英文摘要：
PNAS doi: 10.1073/pnas.1006563107
Transgenic rhesus monkeys produced by gene transfer into early-cleavage–stage embryos using a simian immunodeficiency virus-based vector
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
aKunming Primate Research Center and
bKunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, People's Republic of China;
cKunming Biomed International and
dNational Engineering Research Center of Biomedicine and Animal Science, Kunming 650051, People's Republic of China;
eInstitute of Zoology, Chinese Academy of Sciences, Beijing 100860, People's Republic of China;
fInstitut National de la Santé et de la Recherche Médicale, U846, and
gPrimaStem Stem Cell and Brain Research Institute, Bron 69500, France;
hUniversité de Lyon, Lyon 69003, France;
iBiotechnology Research Center, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650093, People's Republic of China;
jCenter for Molecular Medicine and Department of Ophthalmology, West China Hospital and
kSichuan University, Chengdu 610065, People's Republic of China; and
lInstitute for Genomic Medicine and
mShiley Eye Center, University of California, San Diego, La Jolla, CA 92093
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.
