The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition
Abstract
Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional and/or genetic disruptions in homocysteine metabolism. The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. This variant, with mild enzymatic deficiency, is associated with an increased risk for neural tube defects and pregnancy complications and with a decreased risk for colon cancer and leukemia. Although many studies have reported that this variant is also a risk factor for vascular disease, this area of investigation is still controversial. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. To investigate the in vivo pathogenetic mechanisms of MTHFR deficiency, we generated mice with a knockout of MTHFR: Plasma total homocysteine levels in heterozygous and homozygous knockout mice are 1.6- and 10-fold higher than those in wild-type littermates, respectively. Both heterozygous and homozygous knockouts have either significantly decreased S-adenosylmethionine levels or significantly increased S-adenosylhomocysteine levels, or both, with global DNA hypomethylation. The heterozygous knockout mice appear normal, whereas the homozygotes are smaller and show developmental retardation with cerebellar pathology. Abnormal lipid deposition in the proximal portion of the aorta was observed in older heterozygotes and homozygotes, alluding to an atherogenic effect of hyperhomocysteinemia in these mice.
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Cited by
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Neural tube defects and folate: case far from closed
Blom, H. J., Shaw, G. M., den Heijer, M., & Finnell, R. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1986 · Cited by 562
Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease
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Metadata
- Authors
- Chen, Z.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-03-01
- Volume
- 10
- Issue
- 5
- Pages
- 433-443
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2140483277
- Cited by
- 607
- References
- 50
- FWCI
- 15.71
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. https://app.cochat.ai/papers/10.1093/hmg/10.5.433
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- Chen, Z. (2001). Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Human Molecular Genetics. https://doi.org/10.1093/hmg/10.5.433
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