Slc22a5 haploinsufficiency does not aggravate the phenotype of the long-chain acyl-CoA dehydrogenase KO mouse.
Acyl-CoA Dehydrogenase, Long-Chain
/ deficiency
Animals
Cardiomyopathies
Carnitine
/ analogs & derivatives
Disease Models, Animal
Fatty Acids
/ metabolism
Female
Haploinsufficiency
Hyperammonemia
Lipid Metabolism
/ drug effects
Liver
/ metabolism
Male
Mice
Mice, Knockout
Muscular Diseases
Myocardium
/ metabolism
Phenotype
Solute Carrier Family 22 Member 5
/ genetics
biosynthesis
carnitine
fatty acid oxidation disorders
haploinsufficiency
modifier
Journal
Journal of inherited metabolic disease
ISSN: 1573-2665
Titre abrégé: J Inherit Metab Dis
Pays: United States
ID NLM: 7910918
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
12
09
2019
revised:
22
11
2019
accepted:
11
12
2019
pubmed:
18
12
2019
medline:
24
8
2021
entrez:
18
12
2019
Statut:
ppublish
Résumé
Secondary carnitine deficiency is commonly observed in inherited metabolic diseases characterised by the accumulation of acylcarnitines such as mitochondrial fatty acid oxidation (FAO) disorders. It is currently unclear if carnitine deficiency and/or acylcarnitine accumulation play a role in the pathophysiology of FAO disorders. The long-chain acyl-CoA dehydrogenase (LCAD) KO mouse is a model for long-chain FAO disorders and is characterised by decreased levels of tissue and plasma free carnitine. Tissue levels of carnitine are controlled by SLC22A5, the plasmalemmal carnitine transporter. Here, we have further decreased carnitine availability in the LCAD KO mouse through a genetic intervention by introducing one defective Slc22a5 allele (jvs). Slc22a5 haploinsufficiency decreased free carnitine levels in liver, kidney, and heart of LCAD KO animals. The resulting decrease in the tissue long-chain acylcarnitines levels had a similar magnitude as the decrease in free carnitine. Levels of cardiac deoxycarnitine, a carnitine biosynthesis intermediate, were elevated due to Slc22a5 haploinsufficiency in LCAD KO mice. A similar increase in heart and muscle deoxycarnitine was observed in an independent experiment using Slc22a5
Identifiants
pubmed: 31845336
doi: 10.1002/jimd.12204
pmc: PMC7205564
mid: NIHMS1583719
doi:
Substances chimiques
Fatty Acids
0
Slc22a5 protein, mouse
0
Solute Carrier Family 22 Member 5
0
acylcarnitine
0
Acyl-CoA Dehydrogenase, Long-Chain
EC 1.3.8.8
Carnitine
S7UI8SM58A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
486-495Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK113172
Pays : United States
Informations de copyright
© 2019 SSIEM.
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