Author ORCID Identifier

https://orcid.org/0000-0002-8670-5129

Year of Publication

2022

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Arts and Sciences

Department/School/Program

Biology

First Advisor

Dr. Ashley W. Seifert

Abstract

The outcome of tissue repair varies across species. Vertebrates such as salamanders have the ability to not only heal scar-free but also completely regenerate lost appendages. In contrast, most mammals heal their wounds with fibrotic scarring. Understanding the key drivers of these divergent injury responses remains a major unanswered question in animal biology. Previous work with the Murphy’s Roth Large (MRL/MpJ) inbred mouse strain suggested they have the ability to rapidly close small (2mm) ear holes. While this ability was originally published as an example of regeneration, subsequent work by other groups suggested that it might represent something more akin to hyper-fibrosis. Thus, the ability of MRL/MpJ mice to heal ear hole punches by regeneration or via fibrotic repair (scarring) remains unresolved. The purpose of this study was to analyze ear hole closure in the MRL/MpJ strain across a range of hole sizes and to characterize the healing process. Moreover, I tested multiple hypotheses that could explain the rapid closure of small ear holes, including MRL/MpJ mice exhibit enhanced cell proliferation, increased ECM gene expression, synthesis, and deposition, and that they exhibit hyperinflammation compared to control outbred strains. We found marginal, albeit weak, support for all three hypotheses supporting faster closure of ear punch injuries but did not find evidence of tissue regeneration.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2022.320

Funding Information

This study was supported by the two National Institutes of Health Grants (NIAMS – R01AR070313) in 2017 and (NIDCR – R21DE028070) started in 2019.

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