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Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system.

Publication ,  Journal Article
Lim, KC; Lakshmanan, G; Crawford, SE; Gu, Y; Grosveld, F; Engel, JD
Published in: Nat Genet
June 2000

Mouse embryos deficient in Gata3 die by 11 days post coitum (d.p.c.) from pathology of undetermined origin. We recently showed that Gata3-directed lacZ expression of a 625-kb Gata3 YAC transgene in mice mimics endogenous Gata3 expression, except in thymus and the sympathoadrenal system. As this transgene failed to overcome embryonic lethality (unpublished data and ref. 3) in Gata3-/- mice, we hypothesized that a neuroendocrine deficiency in the sympathetic nervous system (SNS) might cause embryonic lethality in these mutants. We find here that null mutation of Gata3 leads to reduced accumulation of Th (encoding tyrosine hydroxylase, Th) and Dbh (dopamine beta-hydroxylase, Dbh) mRNA, whereas several other SNS genes are unaffected. We show that Th and Dbh deficiencies lead to reduced noradrenaline in the SNS, and that noradrenaline deficiency is a proximal cause of death in mutants by feeding catechol intermediates to pregnant dams, thereby partially averting Gata3 mutation-induced lethality. These older, pharmacologically rescued mutants revealed abnormalities that previously could not be detected in untreated mutants. These late embryonic defects include renal hypoplasia and developmental defects in structures derived from cephalic neural crest cells. Thus we have shown that Gata3 has a role in the differentiation of multiple cell lineages during embryogenesis.

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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

June 2000

Volume

25

Issue

2

Start / End Page

209 / 212

Location

United States

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Trans-Activators
  • Sympathetic Nervous System
  • RNA, Messenger
  • Pregnancy
  • Phenotype
  • Norepinephrine
  • Neural Crest
  • Mice, Knockout
  • Mice
 

Citation

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Lim, K. C., Lakshmanan, G., Crawford, S. E., Gu, Y., Grosveld, F., & Engel, J. D. (2000). Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nat Genet, 25(2), 209–212. https://doi.org/10.1038/76080
Lim, K. C., G. Lakshmanan, S. E. Crawford, Y. Gu, F. Grosveld, and J. D. Engel. “Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system.Nat Genet 25, no. 2 (June 2000): 209–12. https://doi.org/10.1038/76080.
Lim KC, Lakshmanan G, Crawford SE, Gu Y, Grosveld F, Engel JD. Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nat Genet. 2000 Jun;25(2):209–12.
Lim, K. C., et al. “Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system.Nat Genet, vol. 25, no. 2, June 2000, pp. 209–12. Pubmed, doi:10.1038/76080.
Lim KC, Lakshmanan G, Crawford SE, Gu Y, Grosveld F, Engel JD. Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system. Nat Genet. 2000 Jun;25(2):209–212.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

June 2000

Volume

25

Issue

2

Start / End Page

209 / 212

Location

United States

Related Subject Headings

  • Tyrosine 3-Monooxygenase
  • Trans-Activators
  • Sympathetic Nervous System
  • RNA, Messenger
  • Pregnancy
  • Phenotype
  • Norepinephrine
  • Neural Crest
  • Mice, Knockout
  • Mice