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.
Olmstead
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UCLA School of Medicine, Lanterman Developmental Center, Pomona 91769.
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005838:Genotype; D006120:Grooming / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000502:physiology; D009420:Nervous System / Q000254:growth & development*; D009422:Nervous System Diseases / Q000235:genetics / Q000503:physiopathology; D009424:Nervous System Physiological Phenomena