ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Mouse models of cystathionine beta-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 114 citations in OpenAlex.
- Dietary Shift Leads to Venous Thrombosis-Induced Congestive Liver Failure in CBS-Deficient Mice.Journal of inherited metabolic disease · 2025Article
- Homocysteine Attack on Vascular Endothelium-Old and New Features.International journal of molecular sciences · 2025Review
- Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Impact of primary sequence changes on the self-association properties of mammalian cystathionine beta-synthase enzymes.Protein science : a publication of the Protein Society · 2024Article
- Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.Protein science : a publication of the Protein Society · 2024Article
- Article
- Selective HepaticInternational journal of molecular sciences · 2023Article
- Examination of two different proteasome inhibitors in reactivating mutant human cystathionine β-synthase in mice.PloS one · 2023Article
- Emerging roles of cystathionine β-synthase in various forms of cancer.Redox biology · 2022Review
- Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study.Frontiers in nutrition · 2022Article
- Recent development of hydrogen sulfide-releasing biomaterials as novel therapies: a narrative review.Biomaterials translational · 2022Review
- Long-term functional correction of cystathionine β-synthase deficiency in mice by adeno-associated viral gene therapy.Journal of inherited metabolic disease · 2021Article
- The Gasotransmitter Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2021Article
- Analysis of differential neonatal lethality in cystathionine β-synthase deficient mouse models using metabolic profiling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation.Genome biology · 2021Article
- Dietary Regulation of Immunity.Immunity · 2020Review
- Hypermethioninemia Leads to Fatal Bleeding and Increased Mortality in a Transgenic I278T Mouse Model of Homocystinuria.Biomedicines · 2020Article
- Review
- The Cbs Locus Affects the Expression of Senescence Markers and mtDNA Copy Number, but not Telomere Dynamics in Mice.International journal of molecular sciences · 2020Article
- Ferroptosis in Cancer Cell Biology.Cancers · 2020Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Untreated cystathionine beta-synthase (CBS) deficiency in humans is characterized by extremely elevated plasma total homocysteine (tHcy>200 microM), with thrombosis as the major cause of morbidity. Treatment with vitamins and diet leads to a dramatic reduction in thrombotic events, even though patients often still have severe elevations in tHcy (>80 microM). To understand the difference between extreme and severe hyperhomocysteinemia, we have examined two mouse models of CBS deficiency: Tg-hCBS Cbs(-/-) mice, with a mean serum tHcy of 169 microM, and Tg-I278T Cbs(-/-) mice, with a mean tHcy of 296 microM. Only Tg-I278T Cbs(-/-) animals exhibited strong biological phenotypes, including facial alopecia, osteoporosis, endoplasmic reticulum (ER) stress in the liver and kidney, and a 20% reduction in mean survival time. Metabolic profiling of serum and liver reveals that Tg-I278T Cbs(-/-) mice have significantly elevated levels of free oxidized homocysteine but not protein-bound homocysteine in serum and elevation of all forms of homocysteine and S-adenosylhomocysteine in the liver compared to Tg-hCBS Cbs(-/-) mice. RNA profiling of livers indicate that Tg-I278T Cbs(-/-) and Tg-hCBS Cbs(-/-) mice have unique gene signatures, with minimal overlap. Our results indicate that there is a clear pathogenic threshold effect for tHcy and bring into question the idea that mild elevations in tHcy are directly pathogenic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.