Altered presynaptic gene expression in transgenic mice producing dopamine in the pineal gland

Neurotransmitters are known to play an important role in the development of the nervous system. We recently generated transgenic mice that ectopically express tyrosine hydroxylase (TH) and thereby produce dopamine (DA) de nov o in pinealocytes of the pineal gland (PG). The transgenic PG also exhibite d a dramatic decrease in TH-immunoreactive (IR) fibers putatively arising f rom the superior cervical ganglion (SCG) (Cho et al. [1996] Proc Natl Acad Sci USA 93:2862-2866). In the current study, however, we found that there w as no reduction in the number of fibers immunostained for neurofilament pro tein or PGP9.5, markers known to be heavily localized in fibers, despite th e reduction of TH fiber density. Therefore, we investigated whether the dec reased TH-IR fiber density is the consequence of reduced sympathetic innerv ation, or a decrease in TH expression within innervating fibers. Immunohist ochemical, analysis comparing control and transgenic PG demonstrated no app arent differences in numbers of NPY- and aromatic-l-amino acid decarboxylas e (AADC)-IR fibers, indicating that TH expression is decreased in a normal number of innervating fibers. Furthermore, presynaptic neurons in the trans genic SCG showed abnormal and heterogeneous TH immunoreactivity and reduced TH and norepinephrine transporter (NET) mRNA levels. These results show th at ectopic DA production in the PG lowers TH and NET gene expression in the SCG without altering sympathetic innervation to the PG and suggest that th e alteration of target neurotransmitter phenotype may influence gene expres sion of phenotype-specific proteins in projecting neurons. (C) 1999 Wiley-L iss, Inc.