Browsing by Author "Gonzales, Lauren A."
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item A Novel Scanning and Staining Methodology for Visualizing Skeletal and Soft Tissue Using Micro-CT(2023-05) Stalls, Javan A.; Menegaz, Rachel A.; Gonzales, Lauren A.; Lesciotto, Kate M.While there are many forms of radiological imaging that can be used to gather anatomical data from biological specimens, micro-computed tomography (micro-CT) imaging has been the standard for visualizing dense tissue, such as bone, with detailed resolution. However, this imaging modality is not well suited for soft tissues due to their decreased tissue density. This inability to distinguish between soft tissues in CT scans limits our ability to investigate bone-muscle interactions that are thought to stimulate and direct bone modeling during early postnatal development. The goal of this project was to develop a novel CT protocol that incorporates at least two new methods for visualizing soft tissue in CT imaging: iodine staining intended to capture muscle, and ruthenium red staining intended to capture cartilage. The ultimate goal is to enable the creation of an anatomical model that shows the development of both skeletal and soft tissue structures in the crania of neonatal mice from birth to weaning.Item Dental Tissue Changes in Juvenile and Young Adult Mice with Osteogenesis Imperfecta(2022-05) Moore, Jacob C.; Handler, Emma; Menegaz, Rachel A.; Gonzales, Lauren A.Osteogenesis imperfecta (OI) encompasses a heterogeneous family of heritable connective tissue disorders characterized by insufficient or malformed type I collagen protein causing bone fragility, skeletal deformity, and significant dental issues. The most prominent oral characteristic of OI patients, dentinogenesis imperfecta (DI), is characterized by dentition with significant discoloration and structural defects. During normal dental development, specialized cells secrete layers of collagen-rich matrix, which are then mineralized to form the two hard tissues of the tooth – the enamel, the protective tissue that forms the crown of the tooth, and the dentin, which sits internal to the enamel and forms the bulk of the tooth. Importantly, the matrix on which dentin forms is primarily composed of type I collagen. In DI, the secretion of malformed type I collagen in the developing dentin matrix disrupts the normal regulation and organization of this process, causing issues such as hypomineralization, disorganized dentin tubule structure, and dentin hypertrophy. These abnormal structural properties result in the disease phenotype of DI, including discoloration, enamel attrition, and spontaneous dental fractures. This practicum aims to investigate the dental effects of OI by comparing mineralized dental tissue volumes of mice with a type I collagen mutation with wild-type mice with littermates at the juvenile and adult life stages. The animal model under study, the oim mouse (B6C3FE a/a-Col1a2OIM/J), produces abnormal type I collagen due to a mutation in the COL1A2 gene. Mice that are homozygous for this mutation demonstrate a severe OI phenotype, while heterozygotes demonstrate a mild OI phenotype. Prior studies demonstrate that adult oim mice have dental issues similar to those of humans with OI, including reduced dentin tubule density and dentin cross-sectional area. However, the effects of these mutations on dental tissues across the juvenile and young adult periods have not yet been characterized.Item Neurocranial Growth in the OIM Mouse Model of Osteogenesis Imperfecta(2022-05) Husain, Tooba S.; Menegaz, Rachel A.; Handler, Emma; Gonzales, Lauren A.Item Osteogenesis Imperfecta: An analysis of the inner ear development in Mus musculus (house mouse) with comments on hearing quality(2022-05) Huston, Lila A.; Gonzales, Lauren A.; Handler, Emma; Menegaz, Rachel A.; Millar, J. CameronOsteogenesis imperfecta (OI), a developmental disorder of type I collagen, is known to cause hearing loss in ~ 60% of the diseased population. Identified forms include conductive hearing loss (17.4% of OI patients), involving loss of function within the ossicular chain, and sensorineural hearing loss (25.8%), resulting from damage to the cochlea, with the most predominant form being mixed hearing loss (56.8%), involving damage to both the cochlea and ossicles. While OI-related pathologies have largely focused on the middle ear, the pathological appearance of the cochlea (the organ most often compromised in OI-related hearing loss) has gained little focus. In this study, we examine OI-related pathologies on the cochlea in a mouse model for the severe type III OI, to document 1) the morphological differences in the inner ear for adult wildtype mice compared to OI mice in order to determine the anatomy of the diseased state, and 2) intraindividual variation between cochlea of WT and OI mice to determine potential asymmetry in the etiology of the inner ear. We hypothesize that cochlea in mice with OI will have less consistent morphology overall than their WT counterparts due to abnormal growth of the bony capsule. 4 week and 16 week old OIM mice (B6C3Fe a/a-Col1a2oim/J) (n=25) were compared to unaffected wildtype (WT) littermates (n=29) with no known hearing defects. High-resolution micro-CT scans were created for all specimens and 3D models and volumes of the cochlea were generated using 3D Slicer software. Two-tailed Mann-Whitney U-tests were used to investigate differences between 1) right and left ears of the same mouse to examine intraindividual symmetry and 2) differences in volumes between WT and OI cochlea. No major morphologic differences between OI and WT were observed, except for minor areas of higher ossification at the base of the cochlea, mostly within the OI sample. Within WT specimens, we observed little intraindividual difference in the cochlear volume (0-3%). Within OI specimens, significant differences were observed in cochlear volume between right and left ears in the same animal, indicating potential unilateral effects (Mann-Whitney U, p<0.05). When average WT and OI volumes were compared, there was much overlap between the two samples although the OI volumes had a significantly larger range than the WT range (Mann-Whitney U, p=0.704 (w16), p=0.703 (w4)). Overall, our results indicate that mice with OI are much more likely to have evidence of unilateral cochlear volume losses, despite very little difference in overall shape appearance, possibly due to bony capsule encroachment. This find indicates an extremely high potential for sensorineural and mixed hearing loss in OI-bred mice and elucidates at least one mechanism behind how this type of hearing loss might be occurring. Little is known about the pathological appearance of the cochlea in OI, leading to difficulty in managing hearing loss. Further investigation of the etiology and progression of cochlear pathologies will allow for better outcomes in hearing for those patients afflicted with OI-related hearing loss.