Age-dependent alterations in dopamine content, tyrosine hydroxylase activity, and dopamine uptake in the striatum of the weaver mutant mouse.

Mice of different ages and homozygous or heterozygous for the weaver gene (wv) were used to study the time course for the effect of the weaver gene on several striatal dopaminergic parameters. Dopamine uptake was decreased in the homozygous weaver at all ages examined. The deficit in uptake at the earliest age studied, postnatal day 3, was approximately 50% and increased to greater than 70% at older ages. In control mice, dopamine uptake reached a maximum by postnatal day 22, but in homozygous weaver mice, development of uptake activity was curtailed by postnatal day 7. Dopamine content and tyrosine hydroxylase activity were significantly decreased in the homozygous weaver at all ages studied except postnatal days 7 and 10. The magnitude of the deficit in dopamine content ranged from approximately 40% at postnatal days 3 and 5 to about 70% in adults (6 months to 1 year of age). The magnitude of the deficit in tyrosine hydroxylase activity ranged from 40 to 70%. In general, no major differences between heterozygotes and controls were observed for any of the dopaminergic parameters investigated. The results of the present investigation indicate that neurochemical alterations can be observed in the striata of weaver mice as early as postnatal day 3 and raise the possibility that the striatal dopamine transporter may be an early target of the weaver mutation.