Biochemical and behavioral phenotype of AGAT and GAMT deficient mice following long-term Creatine monohydrate supplementation

Metab Brain Dis. 2017 Dec;32(6):1951-1961. doi: 10.1007/s11011-017-0092-3. Epub 2017 Aug 14.


The creatine/phosphocreatine system is essential for cellular phosphate coupled energy storage and production. We investigated the utility of creatine monohydrate supplementation in two different creatine deficient knockout mouse models. Following weaning, female Arginine: Glycine Amidinotransferase (AGAT) and Guanidinoacetate: methyltransferase (GAMT) knockouts and wild type mice were studied based on their genotypes and dietary supplementation (creatine free or 2% creatine monohydrate supplemented diet) for 10 weeks, using a series of behavioral tests and biochemical analyzes. An improved Rota rod performance was observed in both AGAT (p = 0.02) and GAMT knockout mice (p < 0.001) supplemented with 2% creatine. During Morris water maze probe trial, creatine supplemented AGAT knockout mice took less time to reach virtual platform (p = 0.03) and more frequently crossed this area (p = 0.001) than mice on creatine free diet. Similar observations were recorded for GAMT knockout mice. Urinary creatinine concentrations for AGAT (p = 0.001) and GAMT (p = 0.05) knockout mice were increased following creatine supplementation. Creatine supplementation has a potential to improve neuro-muscular coordination, spatial learning in both AGAT and GAMT knockout mice. Long term Creatine supplementation results in increased urine creatinine concentrations indicating improved creatine metabolism in knockout mice.

Keywords: AGAT; Behavior; Biochemical profile; Creatine monohydrate; GAMT; Knockout mouse.

MeSH terms

  • Amidinotransferases / genetics*
  • Animals
  • Creatine / administration & dosage*
  • Diet
  • Guanidinoacetate N-Methyltransferase / genetics*
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / genetics*
  • Motor Skills / drug effects
  • Motor Skills / physiology*
  • Phenotype


  • Guanidinoacetate N-Methyltransferase
  • Amidinotransferases
  • Creatine