Causes and Consequences of Midfacial Hypoplasia in the Yucatan Minipig

尤卡坦小型猪中面部发育不全的原因和后果

• 批准号: 10260379
• 负责人: Michael C Baldwin
• 金额: $ 4.59万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260379
• 关键词: Adipose tissue; Adult; Affect; Air; Air Conditioning; Anatomy; Animal Model; Anterior; Area; Automobile Driving; Biology; Breathing; Cartilage; Cell physiology; Child; Deformity; Dentists; Diabetes Mellitus; Dimensions; Disease; Educational process of instructing; Epiphysial cartilage; Ethmoid bone structure; Face; Failure to Thrive; Family suidae; Fatty acid glycerol esters; Foundations; Genes; Genetic; Goals; Growth; Harvest; Heart Diseases; Histologic; Human; Humidifier; Humidity; Image; Impairment; Infant; Intellectual functioning disability; Jaw; Lead; Life; Location; Lymphoid; Lymphoid Tissue; Mammals; Measures; Memory Loss; Miniature Swine; Modeling; Molecular; Nasal cavity; Nasal septum structure; Nasopharynx; Nose; Operative Surgical Procedures; Orthodontics; Patients; Pharyngeal structure; Physiology; Population; Process; Regulation; Research; Research Project Grants; Respiration Disorders; Respiratory Tract Infections; Role; Scanning; Scientist; Structure; Sudden Death; Surface; Tail; Temperature; Testing; Tissues; Training; Work; Writing; X-Ray Computed Tomography; Zygomatic bone; airway obstruction; career; clinically relevant; craniofacial; effective therapy; innovation; insight; midfacial hypoplasia; novel; premature; prevent; sensor; soft tissue; translational model

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.

项目摘要 这份申请的目的是为了让迈克尔·鲍德温博士成为一名成功的牙医科学家。 颅面生物学领域。除了科学写作、演讲和教学方面的培训外，他还将 开展了一项研究项目，研究面中部发育不全(MFH)的原因和后果。MFH，或 上颌骨、鼻骨和颧骨发育不良，可导致严重畸形，并损害 呼吸。MFH可能危及生命，因此治疗势在必行，但对 MFH的原因及其如何损害呼吸目前的治疗方法有限。患有MFH的猪将成为一种新的， 用于了解MFH原因和后果的临床相关模型。轻度MFH并不少见 在标准猪和小型猪中，但在尤卡坦小型猪中普遍存在，而且更严重，使该品种成为一种 特别有用的模型。猪的MFH与人类的MFH相似，而且猪的体型更像人类， 解剖学和生理学，以及生长发育都比其他动物模型好。这个项目的目标是比较猪 以确定MFH的主要组织原因，并确定结构是否 MFH患者的呼吸道功能受损。目标1将检验这样一种假设，即 鼻中隔软骨含有生长板，在MFH猪中过早骨化，限制了MFH猪的生长 脸部中部。鼻中隔的尾部将从正常和患病的猪身上采集，并 组织学检查生长板的存在或缺失。目标2将检验假设MFH 由于咽部淋巴组织肿大和/或脂肪堆积而导致咽部呼吸道收缩 后外侧咽部。咽部呼吸道的尺寸将使用计算机断层扫描进行测量 (CT)图像和咽后部软组织将进行组织学评估。目标3将测试 假设MFH减少鼻腔表面积，导致体温下降和 湿度调节。将使用CT图像测量鼻腔的尺寸和表面积，以及 空气温度和湿度将通过插入鼻咽部的传感器进行测量。这样做的目的是 该项目将对MFH的原因和后果提供新的见解，这将对 认识和更好地治疗MFH。目标1将确定MFH的主要组织原因，帮助发展 基因靶点和推进颅面生物学领域。目标2将发现MFH在 呼吸道阻塞，允许更有效的治疗来打开呼吸道。目标3将确定MFH是否 影响鼻腔温暖和湿化空气的能力，对管理患者的质量很重要 呼吸和预防呼吸道感染。这个项目将为鲍德温博士的未来奠定基础 从事颅面生物学研究。