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

Metabolic Brain Disease volume 32, pages 1951–1961 (2017)Cite this article

Abstract

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.

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Acknowledgements

The authors are grateful to Prof. Dr. Dirk Isbrandt, University of Hamburg, Hamburg, Germany for donating breeding pairs of AGAT and GAMT mouse models.

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Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Laboratory for Inherited Metabolic Disorders, Medical University of Vienna, Vienna, Austria

    Furhan Iqbal & Gurt Lubec

  2. Institute of Pure and Applied Biology, Zoology Division, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Furhan Iqbal

  3. Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Brauhausgasse 34, A-2235, Himberg, Austria

    Herald Hoeger

  4. Division of Genetics and Genomics, Department of Medicine, Boston Children’s Hospital, Boston, MA, USA

    Olaf Bodamer

Authors
  1. Furhan Iqbal
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  2. Herald Hoeger
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  3. Gurt Lubec
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  4. Olaf Bodamer
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Corresponding author

Correspondence to Furhan Iqbal.

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Financial assistance

This work was part of the PhD (FI). He was sponsored by the Higher Education Commission (HEC) of Pakistan through their overseas PhD fellowship program.

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Authors disclose no conflict of interest.

Electronic supplementary material

Supplementary Figure 1

Comparison of weight gain in the four experimental treatments for AGAT (A) and GAMT (B) mice after 10 weeks of special diet supplementation. (JPEG 104 kb)

11011_2017_92_MOESM2_ESM.doc

Supplementary Figure Table 1 (DOC 38.5 kb)

11011_2017_92_MOESM3_ESM.doc

Supplementary Figure Table 2 (DOC 37.5 kb)

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Iqbal, F., Hoeger, H., Lubec, G. et al. Biochemical and behavioral phenotype of AGAT and GAMT deficient mice following long-term Creatine monohydrate supplementation. Metab Brain Dis 32, 1951–1961 (2017). https://doi.org/10.1007/s11011-017-0092-3

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  • DOI: https://doi.org/10.1007/s11011-017-0092-3

Keywords

  • Creatine monohydrate
  • Knockout mouse
  • AGAT
  • GAMT
  • Behavior
  • Biochemical profile