title: Cystathionine β-synthase-deficient mice thrive on a low-methionine diet.
abstract: Cystathionine β-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.
authors.affiliation: 1Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111, USA. warren.kruger@fccc.edu.
authors.forename: Sapna
authors.initials: S
authors.lastname: Gupta
authors.forename: Stepan B
authors.initials: SB
authors.lastname: Melnyk
authors.forename: Warren D
authors.initials: WD
authors.lastname: Kruger
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D003541:Cystathionine beta-Synthase / Q000172:deficiency*; D004195:Disease Models, Animal; D005260:Female; D006712:Homocystinuria / Q000178:diet therapy*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D008715:Methionine; D003541:Cystathionine beta-Synthase
keywords: alopecia; homocysteine; inborn errors; metabolism; osteoporosis