Disruption of Slc52a3 gene causes neonatal lethality with riboflavin deficiency in mice
Open Access
- 8 June 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 6 (1), 27557
- https://doi.org/10.1038/srep27557
Abstract
Homeostasis of riboflavin should be maintained by transporters. Previous in vitro studies have elucidated basic information about riboflavin transporter RFVT3 encoded by SLC52A3 gene. However, the contribution of RFVT3 to the maintenance of riboflavin homeostasis and the significance in vivo remain unclear. Here, we investigated the physiological role of RFVT3 using Slc52a3 knockout (Slc52a3−/−) mice. Most Slc52a3−/− mice died with hyperlipidemia and hypoglycemia within 48 hr after birth. The plasma and tissue riboflavin concentrations in Slc52a3−/− mice at postnatal day 0 were dramatically lower than those in wild-type (WT) littermates. Slc52a3−/− fetuses showed a lower capacity of placental riboflavin transport compared with WT fetuses. Riboflavin supplement during pregnancy and after birth reduced neonatal death and metabolic disorders. To our knowledge, this is the first report to indicate that Rfvt3 contributes to placental riboflavin transport, and that disruption of Slc52a3 gene caused neonatal mortality with hyperlipidemia and hypoglycemia owing to riboflavin deficiency.This publication has 41 references indexed in Scilit:
- The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectivesOrphanet Journal of Rare Diseases, 2012
- Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia: A key role for hRFT-2 in intestinal riboflavin uptakeBiochimica et Biophysica Acta (BBA) - Biomembranes, 2011
- Brown‐Vialetto‐Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatmentJournal of Inherited Metabolic Disease, 2010
- Identification and Comparative Functional Characterization of a New Human Riboflavin Transporter hRFT3 Expressed in the BrainJournal of Nutrition, 2010
- Mitochondrial fatty acid oxidation disorders: pathophysiological studies in mouse modelsJournal of Inherited Metabolic Disease, 2010
- Brown-Vialetto-Van Laere Syndrome, a Ponto-Bulbar Palsy with Deafness, Is Caused by Mutations in C20orf54American Journal of Human Genetics, 2010
- The Randle cycle revisited: a new head for an old hatAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Brown-Vialetto-Van Laere syndromeOrphanet Journal of Rare Diseases, 2008
- Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolismChemico-Biological Interactions, 2006
- Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Gene-Targeted MicePLoS Genetics, 2005