Cystathionine β-Synthase p.S466L Mutation Causes Hyperhomocysteinemia in Mice
Author Information
Author(s): Gupta Sapna, Wang Liqun, Hua Xiang, Krijt Jakub, Kožich Viktor, Kruger Warren D.
Primary Institution: Fox Chase Cancer Center
Hypothesis
How does the p.S466L mutation in the CBS gene cause disease in vivo?
Conclusion
The p.S466L mutation causes hyperhomocysteinemia by reducing CBS protein levels and enzyme efficiency in vivo.
Supporting Evidence
- The mean serum total homocysteine of Tg-S466L mice was significantly higher than that of hCBS mice.
- Only 48% of Tg-S466L mice had detectable CBS protein in the liver.
- Tg-S466L mice exhibited wide variation in serum homocysteine levels.
Takeaway
A mutation in a gene that helps control a substance in the body led to high levels of that substance in mice, showing how the mutation can cause disease.
Methodology
Mice lacking endogenous CBS were created to express either wild-type or p.S466L human CBS, and serum homocysteine levels were measured after zinc induction.
Limitations
The study primarily focuses on mouse models, which may not fully replicate human conditions.
Participant Demographics
Mice were used in the study, specifically Tg-S466L and Tg-hCBS strains.
Statistical Information
P-Value
p<0.0001
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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