The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.
Amino Acid Metabolism, Inborn Errors
/ genetics
Animals
Arginine
/ metabolism
Brain
/ metabolism
Brain Diseases, Metabolic
/ genetics
Creatine
/ blood
Disease Models, Animal
Gene Knock-In Techniques
Gliosis
/ genetics
Glutaryl-CoA Dehydrogenase
/ deficiency
Humans
Lysine
/ metabolism
Metabolism, Inborn Errors
/ genetics
Rats
Astrogliosis
Cerebral organic aciduria
Glutaric aciduria type I
Hyperammonemia
Lysine degradation
Microglial activation
Journal
Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
04
02
2021
revised:
10
03
2021
accepted:
30
03
2021
pubmed:
10
5
2021
medline:
11
9
2021
entrez:
9
5
2021
Statut:
ppublish
Résumé
Glutaric aciduria type I (GA-I, OMIM # 231670) is an inborn error of metabolism caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH). Patients develop acute encephalopathic crises (AEC) with striatal injury most often triggered by catabolic stress. The pathophysiology of GA-I, particularly in brain, is still not fully understood. We generated the first knock-in rat model for GA-I by introduction of the mutation p.R411W, the rat sequence homologue of the most common Caucasian mutation p.R402W, into the Gcdh gene of Sprague Dawley rats by CRISPR/CAS9 technology. Homozygous Gcdh
Identifiants
pubmed: 33965309
pii: S1096-7192(21)00084-6
doi: 10.1016/j.ymgme.2021.03.017
pii:
doi:
Substances chimiques
Arginine
94ZLA3W45F
Glutaryl-CoA Dehydrogenase
EC 1.3.8.6
Lysine
K3Z4F929H6
Creatine
MU72812GK0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
157-181Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.