Mutations in the SLC2A10 gene cause arterial abnormalities in mice.

Journal Article

AIMS: Glucose transporter 10 (GLUT10), encoded by the SLC2A10 gene, is a member of the class III facilitative glucose transporter family. Mutations in the SLC2A10 gene cause arterial tortuosity syndrome (ATS) in humans. To further study the pathogenesis of the disease, we generated mice carrying GLUT10 mutations. METHODS AND RESULTS: Using a gene-driven N-ethyl-N-nitrosourea (ENU)-mutagenesis approach, we generated mice carrying GLUT10 mutations c.383G>A and c.449C>T, which resulted in missense mutations of glycine to glutamic acid (p.G128E) and serine to phenylalanine (p.S150F), respectively. Both mutant strains appeared normal at birth, gained weight appropriately and survived to adulthood (>18 months). Blood and urine glucose were normal. Echocardiogram and electrocardiogram were also normal and brain magnetic resonance angiography revealed normal cerebral arteries without tortuosity, stenosis/dilatation, or aneurysm. Histopathology revealed thickening and irregular vessel wall shape of large and medium size arteries characterized by markedly increased elastic fibres, both in number and size. There was also intima endothelial hypertrophy and deranged elastic fibres that resulted in disruption of internal elastic lamina in the aorta of older mice. CONCLUSION: Abnormal elastogenesis with early elastic fibre proliferation provides a clue to the pathogenesis of arterial tortuosity in human ATS. Availability of this mouse model will allow testing of the relationship between diabetes and its vascular complications, including diabetic retinopathy, nephropathy and peripheral vascular disease.

Full Text

Duke Authors

Cited Authors

  • Cheng, C-H; Kikuchi, T; Chen, Y-H; Sabbagha, NGA-A-A; Lee, Y-C; Pan, H-J; Chang, C; Chen, Y-T

Published Date

  • February 1, 2009

Published In

Volume / Issue

  • 81 / 2

Start / End Page

  • 381 - 388

PubMed ID

  • 19028722

Pubmed Central ID

  • 19028722

Electronic International Standard Serial Number (EISSN)

  • 1755-3245

Digital Object Identifier (DOI)

  • 10.1093/cvr/cvn319


  • eng

Conference Location

  • England