Causes and Consequences of Midfacial Hypoplasia in the Yucatan Minipig

项目摘要 此应用程序的目的是准备博士迈克尔鲍德温是一个成功的牙医，科学家在 颅面生物学领域。除了科学写作、演讲和教学方面的训练外，他还将进行 一项调查面中部发育不全（MFH）的原因和后果的研究项目。MFH，或 上颌、鼻骨和颧骨发育不全，可导致严重畸形， 呼吸了MFH可能危及生命，使治疗势在必行，但缺乏对MFH的了解， MFH的病因及其如何损害呼吸限制了目前的治疗。患有MFH的猪将成为新的， 了解MFH的原因和后果的临床相关模型。轻度MFH并不少见 在标准猪和小型猪，但它是普遍的，更严重的尤卡坦小型猪，使这个品种， 非常有用的模型。猪的MFH与人类的MFH相似，猪的体型更像人类， 解剖学和生理学，以及其他动物模型的生长。这个项目的目的是比较猪 有和没有MFH，以确定MFH的主要组织原因，并确定结构是否 并且MFH中的气道功能受损。目的1将测试的假设，软骨尾的 鼻中隔软骨含有生长板，其在MFH猪中过早骨化，限制了 中脸将从正常和受影响的猪中收获鼻中隔的尾部， 组织学检查是否有生长板。目标2将检验MFH 由于淋巴组织的增大和/或脂肪在咽部的积聚， 咽后外侧将使用计算机断层扫描测量咽气道的尺寸 (CT)图像和后咽的软组织将进行组织学评价。目标3将测试 假设MFH减少了鼻腔的表面积，导致温度降低， 湿度调节将使用CT图像测量鼻腔的尺寸和表面积， 将通过插入鼻咽的传感器测量空气温度和湿度。这样做的目的是 该项目将提供有关MFH的原因和后果的新见解，这对于 了解并更好地治疗MFH。目的1将确定MFH的主要组织原因， 基因靶点并推进颅面生物学领域。目标2将发现MFH在以下方面的具体作用： 气道阻塞，允许更有效的治疗来打开气道。目标3将确定MFH是否 影响鼻腔温暖和加湿空气的能力，这对管理患者的呼吸质量很重要。 呼吸和预防呼吸道感染。这个项目将作为鲍德温博士未来的基础 颅面生物学的研究生涯

PROJECT ABSTRACT The purpose of this application is to prepare Dr. Michael Baldwin to be a successful dentist-scientist in the field of craniofacial biology. In addition to training in scientific writing, speaking, and teaching, he will carry out a research project investigating the causes and consequences of midfacial hypoplasia (MFH). MFH, or underdevelopment of the upper jaw, nose, and cheek bones, can lead to severe deformity with impairment of breathing. MFH can be life threatening, making treatment imperative, but a lack of understanding about the causes of MFH and how it impairs breathing has limited current treatments. Pigs with MFH will serve as a new, clinically relevant model for understanding the causes and consequences of MFH. Mild MFH is not uncommon in standard pigs and minipigs, but it is universal and more severe in Yucatan minipigs, making this breed an exceptionally useful model. MFH in pigs is similar to MFH in humans, and pigs better resemble humans in size, anatomy and physiology, and growth than other animal models. The objective of this project is to compare pigs with and without MFH to determine the primary tissue cause of MFH, and to determine whether the structure and function of the airway in MFH is compromised. Aim 1 will test the hypothesis that the cartilage tail of the nasal septal cartilage contains a growth plate that ossifies prematurely in MFH pigs, restricting the growth of the midface. The caudal portion of the nasal septum will be harvested from normal and affected pigs and examined histologically for the presence or absence of a growth plate. Aim 2 will test the hypothesis that MFH constricts the pharyngeal airway due to enlargement of lymphoid tissue and/or fat accumulation in the posterolateral pharynx. Dimensions of the pharyngeal airway will be measured using computed tomography (CT) images and the soft tissue of the posterior pharynx will be evaluated histologically. Aim 3 will test the hypothesis that MFH reduces the surface area of the nasal cavity, leading to decreased temperature and humidity regulation. Dimensions and surface area of the nasal cavity will be measured using CT images, and air temperature and humidity will be measured with sensors inserted into the nasopharynx. The aims of this project will provide novel insights about the causes and consequences of MFH that will be important for understanding and better treating MFH. Aim 1 will identify the primary tissue cause of MFH, helping to develop genetic targets and advance the field of craniofacial biology. Aim 2 will discover the specific role of MFH in airway obstruction, allowing for more effective treatments to open the airway. Aim 3 will determine if MFH affects the ability of the nasal cavity to warm and humidify air, important for managing patients’ quality of breathing and preventing respiratory infections. This project will serve as the foundation for Dr. Baldwin’s future research career in craniofacial biology.