Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development

@article{Zhou1995TargetedDO,
  title={Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development},
  author={Qun Zhou and Carol J. Quaife and Richard D. Palmiter},
  journal={Nature},
  year={1995},
  volume={374},
  pages={640-643}
}
TYROSINE hydroxylase catalyses the initial, rate-limiting step in the catecholamine biosynthetic pathway. Catecholamines, which include dopamine, noradrenaline, and adrenaline, are important neurotransmitters and hormones that regulate visceral functions, motor coordination and arousal in adults1. The gene encoding tyro-sine hydroxylase becomes transcriptionally active in developing neuroblasts during mid-gestation of rodent embryos, before the onset of neurotransmission2–6. Here we show that… 
Targeted Disruption of the Tyrosine Hydroxylase Locus Results in Severe Catecholamine Depletion and Perinatal Lethality in Mice (*)
TLDR
Results indicate that TH is essential for survival of the animals during the late gestational development and after birth, and transfer of a human TH transgene into the homozygous mice corrected the mutant phenotype, showing recovery of TH activity by expression of the human enzyme.
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The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously, demonstrates the unequivocal requirement for catecholamines during embryonic development.
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TLDR
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It is demonstrated that dopamine neurotransmission is essential for controlling spontaneous and voluntary movement and associative learning during postnatal development through the nigrostriatal and mesocorticolimbic pathways.
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TLDR
The physiological importance of TH has been evidenced by recent studies showing that targeted disruption of the TH gene results in mid-gestational lethality: about 90% of mutant embryos die between embryonic days 11.5 and 15.5, apparently of cardiovascular failure.
Molecular genetics of tyrosine 3-monooxygenase and inherited diseases.
Tyrosine hydroxylase is expressed during early heart development and is required for cardiac chamber formation.
TLDR
TH is expressed in a dynamic pattern during the primitive heart tube formation and it is a key regulator of the heart patterning, conferring atriogenic identity.
Physiological and genomic consequences of adrenergic deficiency during embryonic/fetal development in mice: impact on retinoic acid metabolism.
TLDR
Evaluation of genomic expression changes in embryonic hearts from adrenergic-deficient and wild-type control mice suggested that RA may be an important downstream mediator of adrenergic action during embryonic heart development and several of the altered genes encode for proteins directly involved in retinoic acid biosynthesis and transport.
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TLDR
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