The inheritance and genetic correlation of tyrosine hydroxylase activities in the substantia nigra and corpus striatum in the C x B recombinant inbred mouse strains.

In mouse, strain differences in the activity of tyrosine hydroxylase (TH) in ventral midbrain dopamine systems of substantia nigra-A10 (SN) region of mouse brain and in a terminal field, the striatum (CS), can be entirely attributed to variations in the number of dopaminergic neurons2. To obtain further information about the complexity of the genetic systems influencing phenotypes for regional TH activity, we examined TH activity in the SN and CS of 7 recombinant inbred (RI) mouse strains, their progenitor strains (BALB/cBy and C57BL/6By), their reciprocal F1 hybrids and a CB6F2 segregating generation. Genetic analysis indicated that TH activity in both brain regions seems unlikely to be controlled by single gene effects. However, the mode of inheritance is presumably not very complex. Estimates of the degree of genetic determination for TH activity in SN and CS were relatively high with significant and positive correlations with respect to either the RI lines (r = 0.82) or the CB6F2 generation (r = 0.53). These positive correlations suggest that some of the genes of two gene sets influencing TH activities in the SN and CS are the same. However, additional non-shared genes may also be present. Assuming that our two measures reflect the number of dopaminergic neurons in SN-A10 area and density of their processes in corpus striatum, our results lead us to the hypothesis that the number of dopaminergic neurons and the axonal arborization of these neurons in the nigrostriatal system are in part under a common genetic control but that other genes may contribute to branching of SN neurons.