INVESTIGATION OF THE PGM5 KNOCKOUT MOUSE AND ITS EFFECT ON MUSCLE FUNCTION

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dc.contributor.advisor Hoffmann, Peter R.
dc.contributor.author Wright, Ryan D.
dc.contributor.department Cell and Molecular Biology
dc.date.accessioned 2024-07-02T23:41:50Z
dc.date.available 2024-07-02T23:41:50Z
dc.date.issued 2024
dc.description.degree M.S.
dc.identifier.uri https://hdl.handle.net/10125/108343
dc.subject Cellular biology
dc.subject Biology
dc.subject Genetics
dc.subject Cardiovascular
dc.subject Cell Biology
dc.subject Genetics
dc.subject Muscular Health
dc.title INVESTIGATION OF THE PGM5 KNOCKOUT MOUSE AND ITS EFFECT ON MUSCLE FUNCTION
dc.type Thesis
dcterms.abstract Abstract The phosphoglucomutase (PGM) family of proteins is composed of five members that have a similar predicted structure containing four distinct domains. In humans and mice, this protein family includes PGM1, PMG2, PGM2L1, PGM3, and PGM5, many of which have been implicated in catalyzing reactions involved in glycogenesis. PGM5 is most closely related to PGM1 in terms of amino acid sequence. However, PGM5 appears to lack enzymatic activity and instead has been shown to localize to cytoskeletal structural complexes. A PGM5 whole animal (with CMV-Cre) knockout (KO) mouse model was developed to determine the biological role of this protein, and we found that mice developed similar to wild-type (WT) controls with no apparent phenotype in development. A Western blot of different tissues showed particularly high levels of PGM5 in cardiac, aortic, and skeletal muscle tissues and a confirmed absence of protein in KO tissues. Given the high expression in these muscle tissues, we subjected the KO and WT control mice to a treadmill critical speed test to evaluate potential differences in exercise tolerance. We found that KO mice exhibit a significantly lower critical speed compared to age matched WT mice, suggesting an impairment in muscle oxidative metabolism. The PGM5 heterozygous mice appear to exhibit a critical speed closer to the WT mice than that of the KO mice, suggesting that one functional PGM5 allele was sufficient for mice to maintain muscle function. These experiments suggest that PGM5 expression is not required for embryogenesis in mice but may impair muscle tissue in the heart for optimal physical activity. Further investigations into heart muscle strength and tolerance to exercise needs to be undertaken along with cell biology experiments to determine the precise role within muscle cells of this PGM family member.
dcterms.extent 31 pages
dcterms.language en
dcterms.publisher University of Hawai'i at Manoa
dcterms.rights All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
dcterms.type Text
local.identifier.alturi http://dissertations.umi.com/hawii:12157
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