PDF(Pubmed)
Abstract：
Greg Lemke\'s laboratory was one of the pioneers of research into the TAM family of receptor tyrosine kinases (RTKs). Not only was Tyro3 cloned in his laboratory, but his group also extensively studied mice knocked out for individual or various combinations of the TAM RTKs Tyro3, Axl, and Mertk. Here we primarily focus on one of the paralogs-MERTK. We provide a historical perspective on rodent models of loss of Mertk function and their association with retinal degeneration and blindness. We describe later studies employing mouse genetics and the generation of newer knockout models that point out incongruencies with the inference that loss of MERTK-dependent phagocytosis is sufficient for severe, early-onset photoreceptor degeneration in mice. This discussion is meant to raise awareness with regards to the limitations of the original Mertk knockout mouse model generated using 129 derived embryonic stem cells and carrying 129 derived alleles and the role of these alleles in modifying Mertk knockout phenotypes or even displaying Mertk-independent phenotypes. We also suggest molecular approaches that can further Greg Lemke\'s scintillating legacy of dissecting the molecular functions of MERTK-a protein that has been described to function in phagocytosis as well as in the negative regulation of inflammation.
摘要：
GregLemke的实验室是受体酪氨酸激酶（RTK）TAM家族研究的先驱之一。不仅在他的实验室克隆了Tyro3,但是他的小组还广泛研究了敲除TAMRTKsTyro3，Axl，还有Mertk.在这里，我们主要集中在一个旁系物-MERTK。我们提供了有关Mertk功能丧失的啮齿动物模型及其与视网膜变性和失明的关联的历史观点。我们描述了采用小鼠遗传学和新一代敲除模型的后来研究，这些模型指出了与MERTK依赖性吞噬作用的丧失足以严重，小鼠早发性光感受器变性。本讨论旨在提高对使用129个衍生胚胎干细胞产生并携带129个衍生等位基因的原始Mertk敲除小鼠模型的局限性的认识,以及这些等位基因在修饰Mertk敲除表型或甚至显示Mertk非依赖性表型中的作用。我们还提出了分子方法，可以进一步研究GregLemke的闪烁遗产，即解剖MERTK-一种已被描述在吞噬作用以及炎症的负调节中起作用的蛋白质的分子功能。
