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: 10411557
• 负责人: Michael C Baldwin
• 金额: $ 2.75万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-02 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10411557
• 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 此申请的目的是准备迈克尔·鲍德温博士成为 颅面生物学领域，除了培训科学写作，讲话和教学外 研究了一个研究项目，该项目调查了中期下降疾病（MFH）的原因和同意。 上颌，鼻子和cheeek骨头的发育不足可能会导致严重畸形，因为 呼吸。 MFH的原因及其如何损害Breating的原因有限。 用于理解MFH的原因和后果的临床相关模型。 在标准的猪和迷人中，但它是大学的普遍性，在尤卡坦迷人中更为严重，使该品种成为Ann 猪中的MFH非常有用。 与其他模型相比，解剖学和生理学和生长。 与并确定MFH的主要组织原因，并确定结构是否 MFH中气道的功能受到损害。 鼻中隔软骨包含一个生长板，可在MFH猪中渗透过早，从而限制 中间的鼻中隔膜的尾部部分将从正常和猪中收获 在组织学上检查的存在或不存在生长板。 由于淋巴组织的扩大和/或脂肪在您中的积累而限制了伴侣气道 后侧面的配对尺寸将使用计算机断层 （CT）图像和后对的软组织将通过组织学评估。 MFH降低了鼻腔表面积的假设，导致温度降低和 湿度调节。 空气温度和湿度将用插入nasporynx的传感器进行测量。 项目提供有关MFH的原因和同意的新颖见解，这对 理解和更好地治疗MFH。 遗传靶标并推进颅面生物学领域。 气道阻塞，使更有效的治疗方法可以打开气道。 影响鼻腔温暖和加湿空气的能力，对于管理患者的质量很重要 breat和防止呼吸中的无情。 颅面生物学研究职业。