Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase.
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.
Rios
M
M
Departments of Neuroscience and Anatomy and Cell Biology, Tufts University Medical School, Boston, Massachusetts 02111, USA.
Habecker
B
B
Sasaoka
T
T
Eisenhofer
G
G
Tian
H
H
Landis
S
S
Chikaraishi
D
D
Roffler-Tarlov
S
S
D000311:Adrenal Glands / Q000378:metabolism; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis*; D002678:Chimera; D003342:Corpus Striatum / Q000378:metabolism; D003433:Crosses, Genetic; D004298:Dopamine / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005091:Exons; D005260:Female; D005728:Ganglia, Sympathetic / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D006580:Genetic Carrier Screening; D015698:Genomic Library; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015183:Restriction Mapping; D012867:Skin / Q000378:metabolism; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D014442:Monophenol Monooxygenase; D004298:Dopamine