Ablating the Transporter Sodium-Dependent Dicarboxylate Transporter 3 Prevents Leukodystrophy in Canavan Disease Mice.

Wang, Yan; Hull, Vanessa; Sternbach, Sarah; Popovich, Brad; Burns, Travis; McDonough, Jennifer; Guo, Fuzheng; Pleasure, David · Ann Neurol · 2021

basic_science · Level V

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Abstract

Canavan disease is caused by ASPA mutations that diminish brain aspartoacylase activity, and it is characterized by excessive brain storage of the aspartoacylase substrate, N-acetyl-l-aspartate (NAA), and by astroglial and intramyelinic vacuolation. Astroglia and the arachnoid mater express sodium-dependent dicarboxylate transporter (NaDC3), encoded by SLC13A3, a sodium-coupled transporter for NAA and other dicarboxylates. Constitutive Slc13a3 deletion in aspartoacylase-deficient Canavan disease mice prevents brain NAA overaccumulation, ataxia, and brain vacuolation. ANN NEUROL 2021;90:845-850.

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