| First Author | Stroobants S | Year | 2008 |
| Journal | Behav Brain Res | Volume | 189 |
| Issue | 2 | Pages | 306-16 |
| PubMed ID | 18336930 | Mgi Jnum | J:133202 |
| Mgi Id | MGI:3778095 | Doi | 10.1016/j.bbr.2008.01.008 |
| Citation | Stroobants S, et al. (2008) Early signs of neurolipidosis-related behavioural alterations in a murine model of metachromatic leukodystrophy. Behav Brain Res 189(2):306-16 |
| abstractText | Arylsulfatase A (ASA)-deficient mice represent an animal model for the lysosomal storage disorder metachromatic leukodystrophy (MLD). Although the model has been applied in pathophysiological and therapeutic studies, the behavioural phenotype of ASA(-/-) mice is only partially characterized, and the most decisive outcome measures for therapy evaluation only emerge beyond 1 year of age. Presently, ASA(-/-) mice and ASA(+/-) control mice were studied at 6 and 12 months of age on an extensive battery including tests of neuromotor ability, exploratory behaviour, and learning and memory. Overt signs of ataxia were not observed in 6-month-old ASA(-/-) mice, but quantitative gait analysis during open-field exploration revealed that ASA(-/-) mice displayed increased hind base width and increased stride lengths for all paws. Their covert motor incoordination was evident in a correlation analysis which unveiled decreased harmonisation of concurrent gait parameters. For example, while ASA(+/-) controls demonstrated substantial convergence of front and hind base width (r=0.54), these variables actually diverged in ASA(-/-) mice (r=-0.37). Furthermore, various behavioural observations indicated emotional alterations in ASA(-/-) mice. Six-month-old ASA(-/-) mice also showed decreased response rates in scheduled operant responding. The present findings could provide relevant behavioural outcome measures for further use of this murine MLD model in preclinical studies. |
