Cystathionine β-synthase-deficient mice thrive on a low-methionine diet

FASEB J. 2014 Feb;28(2):781-90. doi: 10.1096/fj.13-240770. Epub 2013 Nov 4.


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.

Keywords: alopecia; homocysteine; inborn errors; metabolism; osteoporosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Animals
  • Cystathionine beta-Synthase / deficiency*
  • Disease Models, Animal
  • Female
  • Homocystinuria / diet therapy*
  • Male
  • Methionine / administration & dosage
  • Methionine / therapeutic use*
  • Mice
  • Mice, Knockout


  • Methionine
  • Cystathionine beta-Synthase