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Published on: December 2, 2014
Knockout of ERK5 causes multiple defects in placental and embryonic development
Lijun Yan1, Julia Carr, Peter R Ashby
1MRC Protein Phosphorylation Unit, University of Dundee, Dundee, DD1 5EH, UK. l.yan@dundee.ac.uk
Background:
ERK5 is a member of the mitogen activated protein kinase family activated by certain mitogenic or stressful stimuli in cells, but whose physiological role is largely unclear.
Results:
To help determine the function of ERK5 we have used gene targeting to inactivate this gene in mice. Here we report that ERK5 knockout mice die at approximately E10.5. In situ hybridisation for ERK5, and its upstream activator MKK5, showed strong expression in the head and trunk of the embryo at this stage of development. Between E9.5 and E10.5, multiple developmental problems are seen in the ERK5-/- embryos, including an increase in apoptosis in the cephalic mesenchyme tissue, abnormalities in the hind gut, as well as problems in vascular remodelling, cardiac development and placental defects.
Conclusion:
Erk5 is essential for early embryonic development, and is required for normal development of the vascular system and cell survival.
Insights
Extracellular signal-regulated kinase 5 (ERK5) is vital for embryonic development. ERK5 knockout mice exhibit developmental defects and embryonic lethality around day 10.5, underscoring its essential role.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Extracellular signal-regulated kinase 5 (ERK5) is part of the mitogen-activated protein kinase family.
- ERK5 is activated by mitogenic or stressful stimuli.
- The precise physiological function of ERK5 in cellular processes remains largely undetermined.
Purpose of the Study:
- To elucidate the physiological function of ERK5 in mammalian development.
- To investigate the consequences of ERK5 gene inactivation in vivo.
Main Methods:
- Gene targeting was employed to create ERK5 knockout mice (ERK5-/-).
- In situ hybridization was used to analyze the expression patterns of ERK5 and its activator MKK5.
- Embryonic development was monitored from E9.5 to E10.5 for morphological and cellular abnormalities.
Main Results:
- ERK5 knockout mice exhibited embryonic lethality around embryonic day 10.5 (E10.5).
- Significant expression of ERK5 and MKK5 was observed in the embryonic head and trunk at E10.5.
- ERK5-/- embryos displayed increased apoptosis in cephalic mesenchyme, hindgut abnormalities, and defects in vascular remodeling, cardiac development, and placental formation.
Conclusions:
- ERK5 is indispensable for early embryonic development in mice.
- The study highlights ERK5's critical role in vascular system development.
- ERK5 is essential for maintaining cell survival during embryogenesis.
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