Understanding the pathophysiology of Keutel Syndrome: A path towards cure

Keutel综合征（KS）是由MGP基因突变引起的一种罕见的遗传性疾病。KS的主要特征包括先天性面部畸形，交叉咬合和严重的呼吸系统并发症，这可能导致过早死亡。我们对MGP缺陷小鼠（KS的忠实模型）的研究表明，软骨组织中的病理性矿物质沉积（异位钙化）是导致这些异常的主要原因。目前，只有对症治疗，这往往不能防止KS病理的进展。我们缺乏对MGP如何预防各种软骨病理性钙化的了解。这种信息的缺乏严重阻碍了KS患者的新药开发和治疗策略的过程。我们将使用尖端的遗传学和分析技术来解决这一知识缺口。这项使用转基因小鼠和斑马鱼模型的机制研究将确定MGP中预防异常软骨钙化所需的相关功能域，并提供与主要KS性状相关的矿物质积累关键部位的性质信息。了解MGP作为矿化抑制剂的作用机制将对KS患者的治疗具有重要意义。

Keutel Syndrome (KS) is a rare genetic disease caused by mutations in MGP gene. The major KS traits include inborn facial disfigurements, cross-bites and serious respiratory complications, which may lead to premature deaths. Our studies on MGP-deficient mice, a faithful model of KS, show that pathologic mineral deposition (ectopic calcification) in cartilaginous tissues is the primary cause underlying these abnormalities. At present only symptomatic treatments are available, which often fail to prevent the progression of KS pathology. Our lack of understanding of how MGP prevents pathologic calcification of various cartilages is still missing. This lack of information is seriously hampering the process of novel drug development and treatment strategies for KS patients. We will use cutting-edge genetics and analytical techniques to address this gap of knowledge.This mechanistic study using genetically modified mouse and zebrafish models will identify the relevant functional domains in MGP required for the prevention of abnormal cartilage calcification and provide information about the nature of the critical sites of mineral accumulation associated with the major KS traits. Understanding the mechanism of action of MGP as a mineralization inhibitor will have important implications for the treatment of KS patients in future.