Knockout of ERK5 causes multiple defects in placental and embryonic development.
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.


CONCLUSIONS
Erk5 is essential for early embryonic development, and is required for normal development of the vascular system and cell survival.
Yan
Lijun
L
MRC Protein Phosphorylation Unit, University of Dundee, Dundee, DD1 5EH, UK. l.yan@dundee.ac.uk
Carr
Julia
J
Ashby
Peter R
PR
Murry-Tait
Victoria
V
Thompson
Calum
C
Arthur
J Simon C
JS
D000005:Abdomen / Q000002:abnormalities / Q000196:embryology; D000818:Animals; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000098:blood supply / Q000201:enzymology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005804:Genes, Lethal / Q000502:physiology; D006257:Head / Q000002:abnormalities / Q000196:embryology; D035002:Lower Extremity / Q000196:embryology; D038061:Lower Extremity Deformities, Congenital / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D048054:Mitogen-Activated Protein Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D010920:Placenta / Q000002:abnormalities* / Q000196:embryology / Q000201:enzymology
D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases