Causes and Consequences of Midfacial Hypoplasia in the Yucatan Minipig

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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.