Ablating the Transporter <scp>Sodium‐Dependent Dicarboxylate Transporter 3</scp> Prevents Leukodystrophy in Canavan Disease Mice
Yan Wang, Vanessa L. Hull, Sarah Sternbach, B. Y. Popovich, Travis Burns, Jennifer McDonough, Fuzheng Guo, David Pleasure
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.
Topics & Concepts
LeukodystrophyTransporterAtaxiaChemistrySodiumEndocrinologyInternal medicineBiochemistryDiseaseNeuroscienceBiologyMedicineGeneOrganic chemistryAdvanced MRI Techniques and ApplicationsElectron Spin Resonance StudiesLanthanide and Transition Metal Complexes