Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Dis Model Mech. 2011 May;4(3):311-7. doi: 10.1242/dmm.006817.
In 2005, several groups identified a single gain-of-function point mutation in the JAK2 kinase that was present in the majority of patients with myeloproliferative neoplasms (MPNs). Since this discovery, much effort has been dedicated to understanding the molecular consequences of the JAK2V617F mutation in the haematopoietic system. Three waves of mouse models have been produced recently (bone marrow transplantation, transgenic and targeted knock-in), which have facilitated the understanding of the molecular pathogenesis of JAK2V617F-positive MPNs, providing potential platforms for designing and validating novel therapies in humans. This Commentary briefly summarises the first two types of mouse models and then focuses on the more recently generated knock-in models.
2005 年，有几个研究小组发现了 JAK2 激酶中的一个单一获得性功能点突变，该突变存在于大多数骨髓增殖性肿瘤（MPN）患者中。自这一发现以来，人们付出了大量努力来了解 JAK2V617F 突变在造血系统中的分子后果。最近已经产生了三波小鼠模型（骨髓移植、转基因和靶向敲入），这有助于理解 JAK2V617F 阳性 MPN 的分子发病机制，并为在人类中设计和验证新疗法提供了潜在的平台。本评论简要总结了前两种类型的小鼠模型，然后重点介绍了最近产生的敲入模型。
