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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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