Lehman Jonathan M, Michaud Edward J, Schoeb Trenton R, Aydin-Son Yesim, Miller Michael, Yoder Bradley K
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Dev Dyn. 2008 Aug;237(8):1960-71. doi: 10.1002/dvdy.21515.
The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can be analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.
近14年前,橡树岭多囊肾(ORPK)小鼠被描述为人类隐性多囊肾病的模型。ORPK小鼠是通过将一个转基因整合到Ift88基因的一个内含子中产生的,从而产生了一个低表达等位基因(Ift88Tg737Rpw)。Ift88Tg737Rpw突变损害了鞭毛内运输(IFT),这是活动和不活动纤毛组装所需的过程。从历史上看,原发性不活动纤毛被认为对人类健康的重要性最小;然而,现在越来越多的人类疾病被归因于纤毛缺陷。重要的是,这些表型中的许多都存在于ORPK小鼠中并且可以进行分析。在这篇综述中,我们重点介绍了使用OPRK小鼠进行的研究以及与人类纤毛疾病共有的表型。此外,我们描述了ORPK小鼠中一种额外的毛囊发育异常表型,这与人类埃利斯-范克雷维尔德综合征和森森布伦纳综合征中出现的外胚层发育异常一起,表明原发性纤毛在皮肤和毛囊中具有未被认识到的作用。