Mutations in the SLC2A10 gene cause arterial abnormalities in mice.
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.
Cheng
Chao-Hung
CH
Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan, Republic of China.
Kikuchi
Tateki
T
Chen
Yen-Hui
YH
Sabbagha
Nagham George Abd-Al-Ahad
NG
Lee
Yi-Ching
YC
Pan
Huei-Ju
HJ
Chang
Chen
C
Chen
Yuan-Tsong
YT
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
D051246:Glucose Transport Proteins, Facilitative; C531462:Slc2A10 protein, mouse; D016212:Transforming Growth Factor beta