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Type: Journal article
Title: A new mouse model of Canavan leukodystrophy displays hearing impairment due to central nervous system dysmyelination
Author: Carpinelli, M.R.
Voss, A.K.
Manning, M.G.
Perera, A.A.
Cooray, A.A.
Kile, B.T.
Burt, R.A.
Citation: Disease Models and Mechanisms, 2014; 7(6):649-657
Publisher: Company of Biologists
Issue Date: 2014
ISSN: 1754-8403
Statement of
Marina R. Carpinelli, Anne K. Voss, Michael G. Manning, Ashwyn A. Perera, Anne A. Cooray, Benjamin T. Kile and Rachel A. Burt
Abstract: Canavan disease is a leukodystrophy caused by mutations in the ASPA gene. This gene encodes the enzyme that converts N-acetylaspartate into acetate and aspartic acid. In Canavan disease, spongiform encephalopathy of the brain causes progressive mental retardation, motor deficit and death. We have isolated a mouse with a novel ethylnitrosourea-induced mutation in Aspa. This mutant, named deaf14, carries a c.516T>A mutation that is predicted to cause a p.Y172X protein truncation. No full-length ASPA protein is produced in deaf14 brain and there is extensive spongy degeneration. Interestingly, we found that deaf14 mice have an attenuated startle in response to loud noise. The first auditory brainstem response peak has normal latency and amplitude but peaks II, III, IV and V have increased latency and decreased amplitude in deaf14 mice. Our work reveals a hitherto unappreciated pathology in a mouse model of Canavan disease, implying that auditory brainstem response testing could be used in diagnosis and to monitor the progression of this disease.
Keywords: Canavan disease; ASPA; aspartoacylase; leukodystrophy; ENU mutagenesis; myelin
Rights: © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
DOI: 10.1242/dmm.014605
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