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Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy
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:...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302977/ https://www.ncbi.nlm.nih.gov/pubmed/34936099 http://dx.doi.org/10.1002/jimd.12470 |
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author | Duran‐Trio, Lara Fernandes‐Pires, Gabriella Grosse, Jocelyn Soro‐Arnaiz, Ines Roux‐Petronelli, Clothilde Binz, Pierre‐Alain De Bock, Katrien Cudalbu, Cristina Sandi, Carmen Braissant, Olivier |
author_facet | Duran‐Trio, Lara Fernandes‐Pires, Gabriella Grosse, Jocelyn Soro‐Arnaiz, Ines Roux‐Petronelli, Clothilde Binz, Pierre‐Alain De Bock, Katrien Cudalbu, Cristina Sandi, Carmen Braissant, Olivier |
author_sort | Duran‐Trio, Lara |
collection | PubMed |
description | 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 Slc6a8 ( Y389C ) 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. |
format | Online Article Text |
id | pubmed-9302977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93029772022-07-22 Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy Duran‐Trio, Lara Fernandes‐Pires, Gabriella Grosse, Jocelyn Soro‐Arnaiz, Ines Roux‐Petronelli, Clothilde Binz, Pierre‐Alain De Bock, Katrien Cudalbu, Cristina Sandi, Carmen Braissant, Olivier J Inherit Metab Dis Original Articles 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 Slc6a8 ( Y389C ) 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. John Wiley & Sons, Inc. 2021-12-26 2022-03 /pmc/articles/PMC9302977/ /pubmed/34936099 http://dx.doi.org/10.1002/jimd.12470 Text en © 2021 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Duran‐Trio, Lara Fernandes‐Pires, Gabriella Grosse, Jocelyn Soro‐Arnaiz, Ines Roux‐Petronelli, Clothilde Binz, Pierre‐Alain De Bock, Katrien Cudalbu, Cristina Sandi, Carmen Braissant, Olivier Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
title | Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
title_full | Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
title_fullStr | Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
title_full_unstemmed | Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
title_short | Creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
title_sort | creatine transporter–deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302977/ https://www.ncbi.nlm.nih.gov/pubmed/34936099 http://dx.doi.org/10.1002/jimd.12470 |
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