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Gupta S , Melnyk SB , Kruger WD
Cystathionine beta-synthase-deficient mice thrive on a low-methionine diet
FASEB J. 2014 Feb;28(2) :781-90
PMID: 24189943    PMCID: PMC3898656    URL: https://www.ncbi.nlm.nih.gov/pubmed/24189943
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Cystathionine beta-synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Previously, our laboratory developed a mouse model of CBS deficiency, TgI278T Cbs(-)/(-) (abbreviated as Cbs(-/-)), characterized by low weight, low adiposity, decreased Scd-1 expression, facial alopecia, and osteoporosis. To determine the potential benefit of a methionine-restricted diet (MRD), we fed Cbs(-/-) and Cbs(+/-) control mice either an MRD or a regular diet (RD) from weaning till 240 d of age. Cbs(-/-) mice fed the MRD had a 77% decrease in tHcy, 28% increase in weight, 130% increase in fat mass, 82% increase in Scd-1 expression, and 10.6% increase in bone density and entirely lacked the alopecia phenotype observed in age-matched Cbs(-/-) mice fed the RD. At the end of the study, Cbs(-/-) mice fed the MRD were phenotypically indistinguishable from Cbs(+/-) mice fed the RD. Notably, whereas the MRD diet was highly beneficial to Cbs(-/-) mice, it had nearly opposite effect on Cbs(+/-) mice. These studies show that a low-methionine diet can correct the phenotypic consequences of loss of CBS and provide a striking example of how genotype and diet can interact to influence phenotype in mammals.
Gupta, Sapna Melnyk, Stepan B Kruger, Warren D eng P30 CA006927/CA/NCI NIH HHS/ R01 GM098772/GM/NIGMS NIH HHS/ CA06927/CA/NCI NIH HHS/ R01GM098772/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't FASEB J. 2014 Feb;28(2):781-90. doi: 10.1096/fj.13-240770. Epub 2013 Nov 4.