Creatine transporter-deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy
Duran-Trio L, Fernandes-Pires G, Grosse J, Soro-Arnaiz I, Roux-Petronelli C, Binz PA, De Bock K, Cudalbu C, Sandi C, Braissant O
Journal of inherited metabolic disease · 12 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Science Foundation
- Government
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Government
- Swiss National Science Foundation
- Grants
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (175778); Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A)
Based on 3 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2021-12-22 · J Inherit Metab Dis · vol. 45 · issue 2 · pp. 278–291
- Publisher
- Springer Science+Business Media
- Cited
- 19 citations · more than 81% of similar papers · 1.5× the field average
- References
- 64 works
- Access
- Open access (hybrid journal) · CC-BY-NC
- Research areas
- Muscle metabolism and nutrition · Muscle Physiology and Disorders · Genetic Neurodegenerative Diseases
- Keywords
- Creatine, Endocrinology, Internal medicine, Medicine, Atrophy, Muscle atrophy
- MeSH
- muscles, cerebellum, animals, humans, rats, cerebellar diseases, muscular atrophy, syndrome, creatine, membrane transport proteins, guanidinoacetate n-methyltransferase
10 authors
From CH
- Lara Durán-Trío · correspondingCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Gabriella Fernandes‐PiresCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Jocelyn GrosseÉcole Polytechnique Fédérale de Lausanne
- Inés Soro-ArnáizETH Zurich; École Polytechnique Fédérale de Lausanne
- Clothilde Roux‐PetronelliCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Pierre‐Alain BinzCentre Hospitalier Universitaire Vaudois; University of Lausanne
Abstract
Creatine (Cr) is a nitrogenous organic acid and plays roles such as fast phosphate energy buffer to replenish ATP, osmolyte, antioxidant, neuromodulator, and as a compound with anabolic and ergogenic properties in muscle. Cr is taken from the diet or endogenously synthetized by the enzymes arginine:glycine amidinotransferase and guanidinoacetate methyltransferase, and specifically taken up by the transporter SLC6A8. Loss-of-function mutations in the genes encoding for the enzymes or the transporter cause creatine deficiency syndromes (CDS). CDS are characterized by brain Cr deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. Among CDS, the X-linked Cr transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different animal models of CTD show reduced brain Cr levels, cognitive deficiencies, and together they cover other traits similar to those of patients. However, motor function was poorly explored in CTD models, and some controversies in the phenotype exist in comparison with CTD patients. Our recently described Slc6a8Y389C knock-in rat model of CTD showed mild impaired motor function, morphological alterations in cerebellum, reduced muscular mass, Cr deficiency, and increased guanidinoacetate content in muscle, although no consistent signs of muscle atrophy. Our results indicate that such motor dysfunction co-occurred with both nervous and muscle dysfunctions, suggesting that muscle strength and performance as well as neuronal connectivity might be affected by this Cr deficiency in muscle and brain.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC).
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