Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, 10029, USA.
Brain Struct Funct. 2010 Mar;214(2-3):91-109. doi: 10.1007/s00429-009-0230-8. Epub 2009 Nov 25.
Transgenic animals are extensively used to study in vivo gene function as well as to model human diseases. The technology for producing transgenic animals exists for a variety of vertebrate and invertebrate species. The mouse is the most utilized organism for research in neurodegenerative diseases. The most commonly used techniques for producing transgenic mice involves either the pronuclear injection of transgenes into fertilized oocytes or embryonic stem cell-mediated gene targeting. Embryonic stem cell technology has been most often used to produce null mutants (gene knockouts) but may also be used to introduce subtle genetic modifications down to the level of making single nucleotide changes in endogenous mouse genes. Methods are also available for inducing conditional gene knockouts as well as inducible control of transgene expression. Here, we review the main strategies for introducing genetic modifications into the mouse, as well as in other vertebrate and invertebrate species. We also review a number of recent methodologies for the production of transgenic animals including retrovirus-mediated gene transfer, RNAi-mediated gene knockdown and somatic cell mutagenesis combined with nuclear transfer, methods that may be more broadly applicable to species where both pronuclear injection and ES cell technology have proven less practical.
转基因动物被广泛用于研究体内基因功能以及模拟人类疾病。生产转基因动物的技术存在于各种脊椎动物和无脊椎动物物种中。老鼠是研究神经退行性疾病最常用的生物。最常用于生产转基因小鼠的技术涉及将转基因体通过原核注射入受精卵或胚胎干细胞介导的基因靶向。胚胎干细胞技术最常用于产生基因缺失突变体（基因敲除），但也可用于引入微妙的遗传修饰，甚至可以在小鼠的内源性基因中进行单个核苷酸的改变。还可以使用方法诱导条件性基因敲除以及转基因表达的诱导控制。在这里，我们回顾了将遗传修饰引入小鼠以及其他脊椎动物和无脊椎动物物种的主要策略。我们还回顾了一些最近用于生产转基因动物的方法，包括逆转录病毒介导的基因转移、RNAi 介导的基因敲低以及体细胞诱变与核转移相结合的方法，这些方法可能更广泛地适用于那些原核注射和胚胎干细胞技术不太实用的物种。
