A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.
Animals
Computational Biology
Disease Models, Animal
Female
Gene Knock-In Techniques
Glomerular Filtration Rate
Glutarates
/ urine
Glutaryl-CoA Dehydrogenase
/ deficiency
Humans
Infant, Newborn
Kidney
/ metabolism
Male
Metabolism, Inborn Errors
/ pathology
Neonatal Screening
Oxidative Phosphorylation
Protein Interaction Maps
Rats
Vacuoles
/ pathology
(68)Ga EDTA
Glutaric aciduria type I
Organic acidurias
Renal toxicity
Tubulopathy
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:
12 2021
12 2021
Historique:
received:
24
08
2021
revised:
21
10
2021
accepted:
22
10
2021
pubmed:
21
11
2021
medline:
29
3
2022
entrez:
20
11
2021
Statut:
ppublish
Résumé
Glutaric aciduria type I (GA-I, OMIM # 231670) is an autosomal recessive inborn error of metabolism caused by deficiency of the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH). The principal clinical manifestation in GA-I patients is striatal injury most often triggered by catabolic stress. Early diagnosis by newborn screening programs improved survival and reduced striatal damage in GA-I patients. However, the clinical phenotype is still evolving in the aging patient population. Evaluation of long-term outcome in GA-I patients recently identified glomerular filtration rate (GFR) decline with increasing age. We recently created the first knock-in rat model for GA-I harboring the mutation p.R411W (c.1231 C>T), corresponding to the most frequent GCDH human mutation p.R402W. In this study, we evaluated the effect of an acute metabolic stress in form of high lysine diet (HLD) on young Gcdh
Identifiants
pubmed: 34799272
pii: S1096-7192(21)00808-8
doi: 10.1016/j.ymgme.2021.10.003
pii:
doi:
Substances chimiques
Glutarates
0
Glutaryl-CoA Dehydrogenase
EC 1.3.8.6
glutaric acid
H849F7N00B
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
287-300Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.