Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in homocysteine metabolism. A common polymorphism in the MTHFR gene (677C→T) can result in the condition hyperhomocysteinemia when concurrent with low dietary folate intake. In several clinical studies, this polymorphism has been associated with low bone mineral density and increased fracture risk. / The MTHFR knockout mouse, a model for human hyperhomocysteinemia, was used to further investigate the bone phenotype associated with this condition by comparing heterozygous mutants to wild-type animals. Effects of a low folate diet were also assessed. / Bone strength was not decreased, and osteoclast numbers were not increased in heterozygotes or due to low folate. Expression levels of several genes involved in protection against oxidative stress were altered in heterozygotes as compared to wild-types. Bone mineral density was decreased and bone architecture changed as a result of low folate intake, especially in heterozygotes. These findings shed light on possible mechanisms of homocysteine toxicity in bone.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82449 |
| Date | January 2005 |
| Creators | Wikholm, Eva |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002207873, proquestno: AAIMR12564, Theses scanned by UMI/ProQuest. |
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