Cardiff School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK.
Brief Funct Genomics. 2010 Jul;9(4):294-303. doi: 10.1093/bfgp/elq010. Epub 2010 May 10.
Some insight into the developmental basis for imprinting specific genes during the evolution of mammals can be gained from conventional gene 'knockout' studies. However, the consequences of full loss of function are often wide-ranging and may obscure the critical, dosage-related phenotype. This review focuses on transgenic techniques employed to alter the dosage of imprinted genes, including the application of bacterial artificial chromosome transgenic mice, in imprinting research. Advantages of dosage-based techniques over conventional knockout studies will be discussed, with examples. Important applications of transgenic mice in imprinting research, including studying gene expression patterns, the identification of imprinting centres and isolating the consequences of altered gene dosage, are reviewed with a particular focus on the imprinted domain on mouse distal chromosome 7.
从哺乳动物进化过程中印记特定基因的发育基础方面可以获得一些认识,这可以通过常规的基因“敲除”研究来实现。然而,完全丧失功能的后果往往是广泛的,可能会掩盖关键的、与剂量相关的表型。本综述重点介绍了用于改变印记基因剂量的转基因技术,包括细菌人工染色体转基因小鼠的应用,在印记研究中的应用。将讨论基于剂量的技术相对于传统敲除研究的优势,并举例说明。本文还特别关注了小鼠远端染色体 7 上的印记域,详细回顾了转基因小鼠在印记研究中的重要应用,包括研究基因表达模式、鉴定印记中心以及分离基因剂量改变的后果。