Date of Award

5-1-2018

Degree Type

Internship Practicum Report

Degree Name

Master of Science

Department

Graduate School of Biomedical Sciences

First Advisor

Rachel Menegaz

Second Advisor

Rustin E. Reeves

Third Advisor

Rehana S. Lovely

Abstract

Osteogenesis imperfecta (OI, or “brittle bone disease”) is a rare disorder that is caused by genetic point mutations (COL1A1/COL1A2) that affect type 1 collagen. In OI type III (severe) patients, limb bones are more susceptible to skeletal fractures and the bones of the craniofacial region are underdeveloped. Some OI type III patients also suffer from dental malocclusions or fractures (dentinogenesis imperfecta, DI). The goals of this project are 1) to describe the facial phenotype in an OI mouse model, to see if this model can be used to test potential behavioral and pharmaceutical interventions; and 2) to determine if diet and masticatory loading affect the development of the craniofacial region in the OI model. The homozygous OI murine (OIM-/-), a mouse strain with a nonlethal recessively inherited mutation of the COL1A2 gene, is a potential model for the human OI type III. OIM-/- and wild type (WT) littermates were raised from weaning (21 days) to adulthood (16 weeks). Digital 3D craniofacial landmarks were taken from in-vivo micro CT scans, and Kuskal-Wallis ANOVAs, along with Mann-Whitney tests, were used to compare centroid size and interlandmark distances among treatment groups. This practicum focuses on the Week 10 mice, with 3 treatment groups: OIMxM, WTxM, and WTxP. We acknowledge that the sample is incomplete due to factors beyond our immediate control, such as OIM-/- survivability. Adolescent OIM-/- mice (week 10) were found to have on average smaller cranial and mandibular centroid sizes compared to WT mice regardless of diet. Week 10 OIM-/- mice also show several morphological similarities to the OI type III human phenotype, such as shortened cranial vault height, shortened jaw length, and altered dental spacing secondary to a shortened tooth row. We conclude that the OIM mouse model shows potential for future investigations of the growth mechanisms underlying the craniofacial presentation of OI. Furthermore, preliminary results suggest that masticatory loading during the early growth period can be used to stimulate craniofacial bone growth and improve bone quality in the OIM mouse model. Future studies will continue to improve sample size by treatment and age groups. The significance of this project is that it will give a better understanding of the role of type 1 collagen and the biomechanical mechanics of craniofacial development, which are important in the search for a new treatment method in OI.

Comments

Ladd, Summer H., The Effect of Diet on Craniofacial Growth in Osteogenesis Imperfecta Mouse Model. Master of Science (Medical Sciences-Anatomy), May 2018.

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