Cystathionine Beta-Synthase-Deficient Mice Thrive on a Low-Methionine Diet

In a study published in 2014, researchers investigated the effects of a methionine-restricted diet (MRD) on mice with Cystathionine β-synthase (CBS) deficiency, a condition leading to elevated serum total homocysteine (tHcy). The CBS-deficient mice (Cbs-/-) and control mice (Cbs+/-) were fed either an MRD or a regular diet (RD) from weaning until 240 days of age. The Cbs-/- mice on the MRD showed significant improvements: a 77% decrease in tHcy, a 28% increase in weight, a 130% increase in fat mass, an 82% increase in Scd-1 expression, a 10.6% increase in bone density, and an absence of the facial alopecia phenotype that was present in Cbs-/- mice on the RD. By the end of the study, the Cbs-/- mice on the MRD were phenotypically similar to the Cbs+/- mice on the RD. Conversely, the MRD had nearly opposite effects on the Cbs+/- mice. This study demonstrated that a low-methionine diet could correct the physical manifestations of CBS deficiency, highlighting the interaction between genotype and diet in determining phenotype.