A new mouse model of Canavan leukodystrophy displays hearing impairment due to central nervous system dysmyelination.

[canavan disease]

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 deaf 14 , carries a c .516 T >A mutation that is predicted to cause a p .Y 172 X protein truncation . No full-length ASPA protein is produced in deaf 14 brain and there is extensive spongy degeneration . Interestingly , we found that deaf 14 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 deaf 14 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 .