A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
Duran-Trio L, Fernandes-Pires G, Simicic D, Grosse J, Roux-Petronelli C, Bruce SJ, Binz PA, Sandi C, Cudalbu C, Braissant O
Scientific reports · 18 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
- 2021-01-15 · Sci Rep · vol. 11 · issue 1 · p. 1636
- Publisher
- Nature Portfolio
- Cited
- 34 citations · more than 97% of similar papers · 5.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 52 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Muscle metabolism and nutrition · Metabolism and Genetic Disorders · Diet and metabolism studies
- Keywords
- Creatine, Internal medicine, Endocrinology, Epilepsy, Transporter, Creatine Monohydrate, Medicine, Biology, Neuroscience, Biochemistry, Gene, Pathology
- MeSH
- brain, animals, humans, rats, brain diseases, metabolic, inborn, disease models, animal, body weight, creatine, nerve tissue proteins, behavior, animal, memory, short-term, base sequence, genotype, mutation, missense, female, male, plasma membrane neurotransmitter transport proteins, gene knock-in techniques, x-linked intellectual disability
10 authors
From CH
- Lara Durán-TríoCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Gabriella Fernandes‐PiresCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Dunja SimičićCentre d'Imagerie BioMedicale; École Polytechnique Fédérale de Lausanne
- Jocelyn GrosseÉcole Polytechnique Fédérale de Lausanne
- Clothilde Roux‐PetronelliCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Stephen J. BruceCentre Hospitalier Universitaire Vaudois; University of Lausanne
Abstract
Creatine is an organic compound used as fast phosphate energy buffer to recycle ATP, important in tissues with high energy demand such as muscle or brain. Creatine is taken from the diet or endogenously synthetized by the enzymes AGAT and GAMT, and specifically taken up by the transporter SLC6A8. Deficit in the endogenous synthesis or in the transport leads to Cerebral Creatine Deficiency Syndromes (CCDS). CCDS are characterized by brain creatine deficiency, intellectual disability with severe speech delay, behavioral troubles such as attention deficits and/or autistic features, and epilepsy. Among CCDS, the X-linked creatine transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different mouse models of CTD were generated by doing long deletions in the Slc6a8 gene showing reduced brain creatine and cognitive deficiencies or impaired motor function. We present a new knock-in (KI) rat model of CTD holding an identical point mutation found in patients with reported lack of transporter activity. KI males showed brain creatine deficiency, increased urinary creatine/creatinine ratio, cognitive deficits and autistic-like traits. The Slc6a8Y389C KI rat fairly enriches the spectrum of CTD models and provides new data about the pathology, being the first animal model of CTD carrying a point mutation.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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