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Mice develop normally in the absence of Smad4 nucleocytoplasmic shuttling

Christine A Biondi1, Debipriya Das, Michael Howell

  • 1The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.

The Biochemical Journal
|February 16, 2007
PubMed

Insights

Smad4 shuttling between the cytoplasm and nucleus is not essential for mouse development. Eliminating the nuclear export signal (NES) in Smad4 does not impede normal embryonic development or tissue homeostasis.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Smad4 partners with R-Smads to activate TGF-beta signaling, crucial for early mouse development.
  • Smad4 null embryos exhibit severe defects in cell proliferation and differentiation, leading to post-implantation lethality.
  • Smad4 shuttles between cytoplasm and nucleus, regulated by NLS and NES, which is thought to be important for TGF-beta signaling.

Purpose of the Study:

  • To investigate the in vivo role of Smad4 nucleocytoplasmic shuttling in embryonic development.
  • To determine if Smad4 nuclear export is essential for normal mouse development and tissue homeostasis.

Main Methods:

  • Gene targeting was used to create two independent mutations in mice to eliminate Smad4 nuclear export.
  • Assessed Smad4 localization in homozygous ES cells and primary keratinocytes.
  • Evaluated developmental outcomes and tissue homeostasis in Smad4 NES mutant mice.

Main Results:

  • Mutations designed to eliminate Smad4 nuclear export resulted in increased nuclear Smad4 levels in cells.
  • Smad4 expression levels and transcriptional activation capabilities were unaffected by the mutations.
  • Mice lacking the Smad4 NES developed normally, even when carrying one Smad4 null allele.

Conclusions:

  • Smad4 nucleocytoplasmic shuttling is not required for embryonic development in mice.
  • The continuous shuttling of Smad4 is dispensable for tissue homeostasis in healthy adult mice.

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