Mutant mice are described which have a n early developing locomotor difficulty accompanied by definite neuronal changes in the central nervous system. They develop head tremors during the second postnatal week and later action tremors while walking. Seizures occur spontaneously and ran be induced by stimulation. By the third or fourth week, they lose the righting reflex. The most apparent neuropathologic sign is the progressive development o f nuclear hyperchromasia, especially in the largest neurons of the spinal cord and brain stem. Purkinje cells of the cerebellum are similarly affected. Hyperchromasia occurs in single, isolated neurons scattered throughout the central nervous system, as well as in groups of cells which comprise a brain stem nucelus. Lipofuscin pigment in quantities comparable to that i n neurons of 12 months old mice was found i n neurons with hyperchromatic nuclei as early as five weeks of age, a n observation which suggests that premature aging might be occurring in the mutant's central nervous system.A large number of inherited motor defects have been described in mice, and many of these can be attributed to specific mutations (Fuller and Wimer, '66). Such mutations, which during early development lead to degeneration of the myeliE sheaths, defective cerebellar development, and degeneration of dorsal root ganglia, cause neurological syndromes, such as convulsions and uncoordinated behavior (Fuller and Wimer, '66).Neuropathologic changes apparently do not exist in some mutants and have not been described in others, and the cause of the behavioral abnormalities either has not been determined or is related to biochemical defects of metabolism not associated with tissue changes in the nervous system.In the mutant group of mice in this study, definite neuronal abnormalities develop throughout the central ncrvous system as the behavioral syndrome grows progressively more severe. Neurons of these affected mice have been compared with those of normal littermates for the presence of' lipofuscin pigment, in an attempt to determine the occurrence of premature aging in the central nervous system of mutant mice.
MATERIALS AND METHODS
Mice
359