Transgenic Research

, Volume 15, Issue 3, pp 393–397

A Glycine N-methyltransferase Knockout Mouse Model for Humans with Deficiency of this Enzyme

  • Zigmund Luka
  • Antonieta Capdevila
  • José M. Mato
  • C. Wagner
Short Communication

DOI: 10.1007/s11248-006-0008-1

Cite this article as:
Luka, Z., Capdevila, A., Mato, J.M. et al. Transgenic Res (2006) 15: 393. doi:10.1007/s11248-006-0008-1

Abstract

Three human cases having mutations in the glycine N-methyltransferase (GNMT) gene have been reported. This enzyme transfers a methyl group from S-adenosylmethionine (SAM) to glycine to form S-adenosylhomocysteine (SAH) and N-methylglycine (sarcosine) and is believed to be involved in the regulation of methylation. All three cases have mild liver disease but they seem otherwise unaffected. To study this further, gnmt deficient mice were generated for the first time. This resulted in the complete absence of GNMT protein and its activity in livers of homozygous mice. Compared to WT animals the absence of GNMT resulted in up to a 7-fold increase of free methionine and up to a 35-fold increase of SAM. The amount of SAH was significantly decreased (3 fold) in the homozygotes compared to WT. The ratio of SAM/SAH increased from 3 in WT to 300 in livers of homozygous transgenic mice. This suggests a possible significant change in methylation in the liver and other organs where GNMT is expressed.

Keywords

enzyme activityglycine N-methyltransferaseknockout; mouseS-adenosylhomocysteineS-adenosylmethionine

Abbreviations

GNMT

glycine N-methyltransferase

SAM

S-adenosylmethionine

SAH

S-adenosylhomocysteine

Copyright information

© Springer 2006

Authors and Affiliations

  • Zigmund Luka
    • 1
  • Antonieta Capdevila
    • 1
  • José M. Mato
    • 1
  • C. Wagner
    • 1
  1. 1.Department of BiochemistryVanderbilt University School of MedicineNashvilleUSA