Neurological and neurobehavioral development of the mutant ‘twitcher’ mouse

Abstract

The present study described the neurological and locomotor development of the mutant ‘twitcher’ mouse ( B57 BL 6 J-twi ), an enzymatically authentic model of globoid cell (Krabbe) leukodystrophy. Comparisons were made on a neurological developmental battery and a series of behavioral tests, including open field, rotorod, and hangtime performance. Homozygous affected ( twi twi , heterozygous carriers ( + twi ) and homozygous normals ( + + ) were compared. Neurological development was slowed in twi twi with some subtler differences between + twi and normals. Twi twi reached all functional milestones except grasp. There was a rapid deterioration of motor indices after 20 days of age. However, most sensory markers were preserved. On hangtime, there were significant differences from normal for both twi twi and + twi at 15 days of age and across the 15–30 day developmental stage, with the + twi males slightly more impaired. On the rotorod, all animals were equally unable to stay on the rod at 15 days of age and neither male nor female twi twi showed significant development. Male + twi lagged significantly behind male + + . In the open field, all groups were equally inactive at 13–15 days and showed similar increases in activity, rearing, and grooming until weaning. All groups peaked immediately after weaning and declined thereafter, with twi twi showing the lowest activity. The data were discussed in terms of the relationship between the human disease and the animal model.