| First Author | Bannerman P | Year | 2018 |
| Journal | Mol Ther | Volume | 26 |
| Issue | 3 | Pages | 793-800 |
| PubMed ID | 29456021 | Mgi Jnum | J:277366 |
| Mgi Id | MGI:6330922 | Doi | 10.1016/j.ymthe.2018.01.002 |
| Citation | Bannerman P, et al. (2018) Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase-Deficient Canavan Disease Mouse Model. Mol Ther 26(3):793-800 |
| abstractText | Canavan disease, a leukodystrophy caused by loss-of-function ASPA mutations, is characterized by brain dysmyelination, vacuolation, and astrogliosis ("spongiform leukodystrophy"). ASPA encodes aspartoacylase, an oligodendroglial enzyme that cleaves the abundant brain amino acid N-acetyl-L-aspartate (NAA) to L-aspartate and acetate. Aspartoacylase deficiency results in a 50% or greater elevation in brain NAA concentration ([NAAB]). Prior studies showed that homozygous constitutive knockout of Nat8l, the gene encoding the neuronal NAA synthesizing enzyme N-acetyltransferase 8-like, prevents aspartoacylase-deficient mice from developing spongiform leukodystrophy. We now report that brain Nat8l knockdown elicited by intracerebroventricular/intracisternal administration of an adeno-associated viral vector carrying a short hairpin Nat8l inhibitory RNA to neonatal aspartoacylase-deficient Aspa(Nur7/Nur7) mice lowers [NAAB] and suppresses development of spongiform leukodystrophy. |
