Slc2a10, encoding the facilitative glucose transporter GLUT10, is a member of the class III facilitative glucose transporter family [2]. It has been implicated in the transport of dehydroascorbic acid [1]. Mutations in this gene are associated with arterial tortuosity syndrome (ATS), a connective tissue disorder. The underlying pathways may involve extracellular matrix formation and mitochondrial function [1]. Genetic models, such as mouse models, are valuable for studying its functions.

In a study, Gulo;Slc2a10 double knock-out mice, deficient in both Slc2a10 and an enzyme for ascorbic acid synthesis, showed mild phenotypic anomalies, compromised extracellular matrix formation, and mitochondrial function in smooth muscle cells, adding evidence that ATS is an ascorbate compartmentalization disorder [1]. Mice carrying GLUT10 missense mutations (c.383G>A and c.449C>T) had thickening and irregular vessel wall shape of large and medium-sized arteries, with increased elastic fibers, intima endothelial hypertrophy, and disruption of the internal elastic lamina in older mice, providing clues to the pathogenesis of arterial tortuosity in human ATS [2]. Also, the SLC2A10 gene polymorphism is an independent risk factor for peripheral arterial disease in type 2 diabetes [3].

In conclusion, Slc2a10 is crucial for processes related to extracellular matrix and mitochondrial function, with its mutations leading to arterial abnormalities. The study of Slc2a10 gene-knockout mouse models has significantly contributed to understanding the pathogenesis of ATS and the role of SLC2A10 in peripheral arterial disease in type 2 diabetes.

References:

1. Boel, Annekatrien, Burger, Joyce, Vanhomwegen, Marine, Essers, Jeroen, Callewaert, Bert. . Slc2a10 knock-out mice deficient in ascorbic acid synthesis recapitulate aspects of arterial tortuosity syndrome and display mitochondrial respiration defects. In Human molecular genetics, 29, 1476-1488. doi:10.1093/hmg/ddaa071. https://pubmed.ncbi.nlm.nih.gov/32307537/

2. Cheng, Chao-Hung, Kikuchi, Tateki, Chen, Yen-Hui, Chang, Chen, Chen, Yuan-Tsong. 2008. Mutations in the SLC2A10 gene cause arterial abnormalities in mice. In Cardiovascular research, 81, 381-8. doi:10.1093/cvr/cvn319. https://pubmed.ncbi.nlm.nih.gov/19028722/

3. Jiang, Yi-Der, Chang, Yi-Cheng, Chiu, Yen-Feng, Chen, Yuan-Tsong, Chuang, Lee-Ming. 2010. SLC2A10 genetic polymorphism predicts development of peripheral arterial disease in patients with type 2 diabetes. SLC2A10 and PAD in type 2 diabetes. In BMC medical genetics, 11, 126. doi:10.1186/1471-2350-11-126. https://pubmed.ncbi.nlm.nih.gov/20735855/