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… 
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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.
Catecholamine Synthesis is Mediated by Tyrosinase in the Absence of Tyrosine Hydroxylase
TLDR
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.
Examining adrenergic roles in development, physiology, and behavior through targeted disruption of the mouse dopamine beta-hydroxylase gene.
Noradrenaline is essential for mouse fetal development
TLDR
It is reported here that in heterozygous mothers, most homozygous embryos died in utero, and only about 5% reached adulthood, suggesting that death might be due to cardiovascular failure.
Early ontogeny of catecholaminergic cell lineage in brain and peripheral neurons monitored by tyrosine hydroxylase-lacZ transgene.
Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission
TLDR
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.
Tyrosine Hydroxylase: Biochemical Properties and Short-term Regulation in vitro and in vivo
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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References

SHOWING 1-10 OF 21 REFERENCES
Noradrenaline is essential for mouse fetal development
TLDR
It is reported here that in heterozygous mothers, most homozygous embryos died in utero, and only about 5% reached adulthood, suggesting that death might be due to cardiovascular failure.
Ontogenetic appearance and disappearance of tyrosine hydroxylase and catecholamines in the rat embryo.
TLDR
Observations suggest that a number of noradrenergic transmitter mechanisms develop simultaneously in the differentiating neuroblast, and the relevance of these results to the elucidation of developmental regulatory mechanisms is discussed.
Regulation of tyrosine hydroxylase mRNA in catecholaminergic cells of embryonic rat: analysis by in situ hybridization.
TLDR
Data from In situ hybridization are consistent with the hypothesis that the microenvironment of the embryonic intestine affects gene expression directly to alter phenotype, and although reserpine administration briefly increases TH mRNA levels, the effect is short-lived and does not alter neurotransmitter phenotypic conversion.
Appearance of catecholamine-synthesizing enzymes during development of rat sympathetic nervous system: possible role of tissue environment.
TLDR
It is concluded that neural crest cells express a noradrenergic phenotype only after leaving the neural crest and that these cells are labile with respect to their neurotransmitter and are capable of transformation in response to environmental stimuli.
Human tyrosine hydroxylase and insulin genes are contiguous on chromosome 11.
TLDR
The localization of TH to the highly polymorphic INS locus provides four new restriction fragment length polymorphisms which should help determine rapidly whether defects in TH are responsible for bipolar affective disorder in the Old Order Amish and other populations.
Proliferation and distribution of cells that transiently express a catecholaminergic phenotype during development in mice and rats.
Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons
Structure of the mouse tyrosine hydroxylase gene.
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice
A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting
TLDR
Germ-line transmission of the inactivated IGF-II gene from male chimaeras yielded heterozygous progeny that were smaller than their ES cell-derived wild-type littermates (about 60% of normal body weight) and these growth-deficient animals were otherwise apparently normal and fertile.
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