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

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_8DAB6587D7CA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism.
Journal
Scientific reports
Author(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
Publication state
Published
Issued date
15/01/2021
Peer-reviewed
Oui
Volume
11
Number
1
Pages
1636
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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 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
Yes
Create date
26/01/2021 15:14
Last modification date
22/09/2021 6:38
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