Mutations in the SLC2A10 gene cause arterial abnormalities in mice

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 GLUT...

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Published in:Cardiovascular research 2009-02, Vol.81 (2), p.381-388
Main Authors: Cheng, Chao-Hung, Kikuchi, Tateki, Chen, Yen-Hui, Sabbagha, Nagham George Abd-Al-Ahad, Lee, Yi-Ching, Pan, Huei-Ju, Chang, Chen, Chen, Yuan-Tsong
Format: Article
Language:English
Subjects:
Animals
Arterial tortuosity syndrome
Arteries - abnormalities
Arteries - pathology
Biological and medical sciences
Cardiology. Vascular system
Elastic Tissue - cytology
Female
Glucose Transport Proteins, Facilitative - genetics
Glucose transporter 10
Male
Medical sciences
Mice
Mice, Inbred C3H
Mutation
SLC2A10
Transforming Growth Factor beta - physiology
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Summary: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.
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvn319