A double-transgenic approach to overexpression of GDNF in the principal target structures of the mesencephalic dopaminergic projection. A, The transgene incorporates a bidirectional promoter, driving expression of LacZ [with a nuclear localization signal (NLS)] in one direction and bp 39–685 of rat GDNF in the other. B, When CaMKIIα-tTA monotransgenic mice are crossed with BiTetO-LacZ-rGDNF monotransgenics, the resulting double transgenics will express rGDNF (and LacZ) only in those brain regions in which CaMKIIα is normally expressed: striatum, cortex, and hippocampus. Expression of GDNF can be suppressed by administration of doxycycline (DOX).