Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4

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Cell Type-specific Gene Expression Profiling in the Mouse Liver
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Cell Type-specific Gene Expression Profiling in the Mouse Liver

Published on: September 17, 2019

H Nishina1, C Vaz, P Billia

  • 1The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Suite 706, Toronto, Ontario M5G 2C1, Canada.

Development (Cambridge, England)
|January 7, 1999
PubMed

Insights

The stress-responsive kinase SEK1/MKK4 is essential for mammalian organogenesis. Disruption of the SEK1 gene causes severe anemia and impaired liver development due to hepatocyte apoptosis.

Area of Science:

  • Cellular biology
  • Developmental biology
  • Genetics

Background:

  • SEK1/MKK4 is a key activator of stress-activated protein kinases (SAPKs/JNKs) in response to cellular stress.
  • SAPKs/JNKs play critical roles in cellular responses to various environmental and internal stimuli.

Purpose of the Study:

  • To investigate the role of SEK1/MKK4 in mammalian development using a genetic approach.
  • To determine the function of SEK1 in organogenesis, particularly liver development.

Main Methods:

  • Homologous recombination was used to disrupt the sek1 gene in mice, creating sek1(-/-) knockout embryos.
  • Embryonic development, including hematopoiesis, vasculogenesis, and hepatogenesis, was analyzed in sek1(-/-) and wild-type embryos.

Main Results:

  • Sek1(-/-) embryos exhibited severe anemia and embryonic lethality between E10.5 and E12.5.
  • While hematopoiesis and vasculogenesis were unaffected, hepatogenesis and liver formation were severely impaired in mutant embryos.
  • Sek1(-/-) liver cells underwent massive apoptosis, leading to a significant reduction in hepatocytes.

Conclusions:

  • This study establishes the first genetic link between stress-responsive kinases and mammalian organogenesis.
  • SEK1/MKK4 provides a critical survival signal for hepatocytes, highlighting its essential role in liver development.

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