A 6.1 KB 5' UPSTREAM REGION OF THE MOUSE TRYPTOPHAN-HYDROXYLASE GENE DIRECTS EXPRESSION OF ESCHERICHIA-COLI LACZ TO MAJOR SEROTONERGIC BRAIN-REGIONS AND PINEAL-GLAND IN TRANSGENIC MICE

Tryptophan hydroxylase (TPH) catalyzes the first step of serotonin bio synthesis in serotonergic neurons and neuroendocrine cells. Serotonin influences diverse vital physiological functions and is thought to pla y an important role in several human psychiatric disorders. To localiz e DNA element(s) important for serotonergic tissue-specific expression of TPH, 6.1 kb of the 5' flanking region of the mouse TPH gene was fu sed to the coding region of the E. coli lacZ gene, and expression of t he resulting fusion gene was analyzed in transgenic mice. The 6.1 kb o f 5' flanking sequence was able to direct the expression of a lacZ rep orter gene to serotonergic tissues in six lines of transgenic mice. A high level of lacZ expression in transgenic mice carrying the fusion g ene was detected in the pineal gland as well as a moderate level of la cZ expression in serotonergic brain regions such as the median and dor sal raphe nuclei, the nuclei raphe magnus and raphe pallidus. In contr ast, a smaller 5' flanking sequence of 1.1 kb directed no detectable s erotonergic tissue-specific lacZ expression in five lines of transgeni c mice. These results presented in this paper suggest first that DNA e lements critical to serotonergic tissue-specific expression reside bet ween -6.1 kb and -1.1 kb of 5' flanking region of the mouse TPH gene, but second that this region confers a restricted tissue-specific expre ssion.