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

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 S...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lara Duran-Trio, Gabriella Fernandes-Pires, Dunja Simicic, Jocelyn Grosse, Clothilde Roux-Petronelli, Stephen J. Bruce, Pierre-Alain Binz, Carmen Sandi, Cristina Cudalbu, Olivier Braissant
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/947e106bf90e4b49b7a6b29e87d3bc28
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:947e106bf90e4b49b7a6b29e87d3bc28
record_format	dspace
spelling	oai:doaj.org-article:947e106bf90e4b49b7a6b29e87d3bc282021-12-02T14:01:32ZA new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism10.1038/s41598-020-80824-x2045-2322https://doaj.org/article/947e106bf90e4b49b7a6b29e87d3bc282021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80824-xhttps://doaj.org/toc/2045-2322Abstract 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 Y389C 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.Lara Duran-TrioGabriella Fernandes-PiresDunja SimicicJocelyn GrosseClothilde Roux-PetronelliStephen J. BrucePierre-Alain BinzCarmen SandiCristina CudalbuOlivier BraissantNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lara Duran-Trio Gabriella Fernandes-Pires Dunja Simicic Jocelyn Grosse Clothilde Roux-Petronelli Stephen J. Bruce Pierre-Alain Binz Carmen Sandi Cristina Cudalbu Olivier Braissant A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
description	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 Y389C 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.
format	article
author	Lara Duran-Trio Gabriella Fernandes-Pires Dunja Simicic Jocelyn Grosse Clothilde Roux-Petronelli Stephen J. Bruce Pierre-Alain Binz Carmen Sandi Cristina Cudalbu Olivier Braissant
author_facet	Lara Duran-Trio Gabriella Fernandes-Pires Dunja Simicic Jocelyn Grosse Clothilde Roux-Petronelli Stephen J. Bruce Pierre-Alain Binz Carmen Sandi Cristina Cudalbu Olivier Braissant
author_sort	Lara Duran-Trio
title	A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
title_short	A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
title_full	A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
title_fullStr	A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
title_full_unstemmed	A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
title_sort	new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/947e106bf90e4b49b7a6b29e87d3bc28
work_keys_str_mv	AT laradurantrio anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT gabriellafernandespires anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT dunjasimicic anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT jocelyngrosse anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT clothilderouxpetronelli anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT stephenjbruce anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT pierrealainbinz anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT carmensandi anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT cristinacudalbu anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT olivierbraissant anewratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT laradurantrio newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT gabriellafernandespires newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT dunjasimicic newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT jocelyngrosse newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT clothilderouxpetronelli newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT stephenjbruce newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT pierrealainbinz newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT carmensandi newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT cristinacudalbu newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism AT olivierbraissant newratmodelofcreatinetransporterdeficiencyrevealsbehavioraldisorderandalteredbrainmetabolism
_version_	1718392156756901888

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

Ejemplares similares