RT Journal Article
SR Electronic
T1 Catecholamine Synthesis is Mediated by Tyrosinase in the Absence of Tyrosine Hydroxylase
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3519
OP 3526
DO 10.1523/JNEUROSCI.19-09-03519.1999
VO 19
IS 9
A1 Rios, Maribel
A1 Habecker, Beth
A1 Sasaoka, Toshikuni
A1 Eisenhofer, Graeme
A1 Tian, Hua
A1 Landis, Story
A1 Chikaraishi, Dona
A1 Roffler-Tarlov, Suzanne
YR 1999
UL http://www.jneurosci.org/content/19/9/3519.abstract
AB Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to l-dihydroxyphenylalanine (l-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant dams. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to l-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines.