DEFECTIVE TOOTH MORPHOGENESIS IN THE IFT88ORPK MUTANT MOUSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 初级纤毛存在于大多数哺乳动物细胞上，但对其在哺乳动物牙列中的功能知之甚少。越来越多的疾病，包括Bardet-Biedl综合征、口腔面部指端综合征I和Ellis-van Creveld综合征，被归因于初级纤毛或基底体功能基因的突变。除了常见的病理，如肾囊肿和骨骼缺陷的发展，这些疾病中的几个也有缺陷的牙齿图案，发育或形态发生。尽管有这些证据表明初级纤毛对牙齿的形态发生很重要，但很少有人致力于了解初级纤毛在哺乳动物牙列中的功能。这个项目的目标是在一种以初级纤毛缺陷为特征的小鼠模型中检查磨牙的成熟情况，Ift88orpk突变小鼠。除了多指、脑积水和肾囊肿等病理改变外，Ift88orpk突变小鼠还会患上异位臼齿。在这个小鼠模型中，磨牙的成熟还没有被研究。对这一小鼠模型的磨牙形态发生和成熟的检查将有助于深入了解初级纤毛在哺乳动物牙齿发育中的作用，以及这些综合征中纤毛功能缺陷如何导致牙齿结构的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary cilia are present on most mammalian cells but their function is poorly understood in mammalian dentition. A growing number of disorders including Bardet-Biedl syndrome, Oral facial digital syndrome I, and Ellis-van Creveld syndrome have been attributed to mutations in genes that function in primary cilia or basal bodies. In addition to common pathologies such as development of renal cysts and skeletal defects, several of these disorders also have defects in tooth patterning, development or morphogenesis. Despite this evidence that primary cilia are important for the morphogenesis of the tooth, little research has been devoted to understanding the function of primary cilia in the mammalian dentition. The goal of this project is to examine the maturation of the molars in a murine model that features defective primary cilia, the Ift88orpk mutant mouse. In addition to pathologies including polydactyly, hydrocephalus and renal cysts, Ift88orpk mutant mice develop an ectopic molar. The maturation of the molars in this mouse model has not been investigated. Examination of molar morphogenesis and maturation in this mouse model will provide insight into the role primary cilia play in mammalian tooth development and how defective cilia function in these syndromes leads to changes in tooth structure.