Neurological and neurobehavioral development of the mutant 'twitcher' mouse

The present study described the neurological and locomotor development of the mutant 'twitcher' mouse (B57BL/6J-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.