title: Mutations in the SLC2A10 gene cause arterial abnormalities in mice.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan, Republic of China.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Cheng
authors.forename: Tateki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Yen-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Nagham George Abd-Al-Ahad
authors.initials: NG
authors.lastname: Sabbagha
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lee
authors.forename: Huei-Ju
authors.initials: HJ
authors.lastname: Pan
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
mesh_terms: D000818:Animals; D001158:Arteries / Q000002:abnormalities* / Q000473:pathology; D004547:Elastic Tissue / Q000166:cytology; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C531462:Slc2A10 protein, mouse; D016212:Transforming Growth Factor beta