Cerebral metabolism in rock and roll rodents.

What is the matter with mice that dance, lurch, stagger, twirl, tremble or totter, quiver or quake, shiver or shake? Such strange activity describes some of the motor manifestations of over 100 strains of mice with neurological mutations (Sidman et aI., 1965; Mouse News Letter, 1982). The behavior it­ self is somewhat nonspecific, since it does not necessarily indicate the anatomical site or patho­ physiological nature of the neurological condition. This abnormal locomotor activity can be the ex­ pression of a genetic disorder manifested at one or more different sites. Not infrequently, the name used to label these neurological mutants is mis­ leading. "Dystonia musculorum," for example, de­ scribes a mouse with hypertonic posturing of limbs and writhing movements of the trunk, but mor­ phologic studies to date suggest it is primarily a dis­ order of sensory nerves. Neurological mutations of mice offer a unique opportunity for studying genetic diseases of the nervous system. Whereas in man many genetic dis­ orders are uncommon-allowing studies on only a limited number of cases-or show delayed, vari­ able, and incomplete phenotypic penetrance, such problems can be largely circumvented by breeding these mice. Most strains have been characterized for the specific abnormal gene locus, and morpho­ logical and biochemical abnormalities have been described in many cases. In more than a few, how­ ever, there is no clear pathological abnormality, de­ spite grossly abnormal behavior. It is in this situa­ tion that metabolic studies are proving to be partic­ ularly useful. Such was the case in studies of the mutant mouse tottering (tgltg). This animal has spontaneous electroencephalographic and be­ havioral seizures as well as ataxia. The seizures are characterized by behavioral arrest and partial motor convulsions. Studies of this mutant with the au­ toradiographic deoxyglucose method revealed re­ stricted activation of certain subcortical thalamic, extrapyramidal, and reticular nuclei, suggesting im­ portant clues to a genetic model of "centrence­ phalic epilepsy" (Nobels and Sidman, 1979).