Date of Award

12-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Microbiology, Immunology, and Biochemistry

Research Advisor

Elizabeth A. Fitzpatrick, PhD

Committee

Marko Radic, PhD; Ae-Kyung, PhD

Keywords

BXD;EAE;Multiple Sclerosis

Abstract

Multiple Sclerosis is an autoimmune inflammatory condition that causes disability, axonal damage in the central nervous system, and eventual paralysis. One of the main risk factors for developing MS is genetics, with recent studies identifying multiple risk alleles associated the major histocompatibility complex. By utilizing the BXD family of mice, we investigated genetic factors that affect a BXD strain’s susceptibility to EAE, an inducible disease model for MS. We induced EAE in several BXD mice strains via an emulsion of complete Freund’s adjuvant and MOG35-55, and then measured disease severity in each strain. From there, we measured incidence rate of EAE, average peak clinical score, average day of disease onset, average length of acute onset, and average end clinical score. Afterwards, we tested EAE severity in the BXD43 mouse by identifying changes in immune cell populations in the spinal cord, changes in cytokines and chemokines, and distribution of the Fc multimer drug M019. Out of 16 strains tested, we identified 6 BXD strains susceptible to developing EAE, and found suggestive evidence of QTLs on chromosomes 5 and 11. We also found that the BXD43 strain expressed an extreme phenotype, categorized by increased immune cell populations in the spinal cord comparable to the B6 EAE model with pertussis toxin. These results suggest the potential for QTLs to exist on chromosomes 5 and 11, though more BXD strains need to be tested. Additionally, the BXD43 strain shows promise as an extreme phenotype model for EAE, which may serve as an effective model for primary progressive multiple sclerosis.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

0009-0002-6051-2182

DOI

10.21007/etd.cghs.2023.0653

Additional Files
2023-038-Danehy-DOA.pdf (188 kB)
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