A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism.

Détails

Ressource 1Télécharger: 2021-SciRep Duran-Trio.pdf (4265.83 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_8DAB6587D7CA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism.
Périodique
Scientific reports
Auteur(s)
Duran-Trio L., Fernandes-Pires G., Simicic D., Grosse J., Roux-Petronelli C., Bruce S.J., Binz P.A., Sandi C., Cudalbu C., Braissant O.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
15/01/2021
Peer-reviewed
Oui
Volume
11
Numéro
1
Pages
1636
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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 Slc6a8 <sup>Y389C</sup> 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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/01/2021 15:14
Dernière modification de la notice
22/09/2021 6:38
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