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The Journal of Neuroscience, May 1, 1999, 19(9):3519-3526

Catecholamine Synthesis is Mediated by Tyrosinase in the Absence of Tyrosine Hydroxylase

Maribel Rios1, Beth Habecker2, Toshikuni Sasaoka3, Graeme Eisenhofer2, Hua Tian2, Story Landis2, Dona Chikaraishi4, and Suzanne Roffler-Tarlov1

1 Departments of Neuroscience and Anatomy and Cell Biology, Tufts University Medical School, Boston, Massachusetts 02111, 2 National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, 3 National Institute of Neuroscience, National Center for Neurology and Psychiatry, Tokyo 187, Japan, and 4 Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710

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.

Key words: catecholamines; tyrosine hydroxylase-null mutation; tyrosinase; tyrosine hydroxylase; tyrosinase and catecholamine synthesis; catecholamines in development; catecholamine synthesis


Copyright © 1999 Society for Neuroscience  0270-6474/99/1993519-08$05.00/0


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