Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2.
Mice lacking both c-Jun-NH(2)-terminal kinases (JNK1 and JNK2) were generated to define their roles in development. Jnk1/jnk2 double mutant fetuses die around embryonic day 11 (E11) and were found to display an open neural tube (exencephaly) at the hindbrain level with reduced apoptosis in the hindbrain neuroepithelium at E9.25. In contrast, a dramatic increase in cell death was observed one day later at E10.5 in both the hindbrain and forebrain regions. Moreover, about 25% of jnk1-/-jnk2+/- fetuses display exencephaly probably due to reduced levels of JNK proteins, whereas jnk1+/-jnk2-/- mice are viable. These results assign both pro- and anti-apoptotic functions for JNK1 and JNK2 in the development of the fetal brain.
Sabapathy
K
K
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030, Vienna, Austria.
Jochum
W
W
Hochedlinger
K
K
Chang
L
L
Karin
M
M
Wagner
E F
EF
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001921:Brain / Q000002:abnormalities / Q000196:embryology; D002455:Cell Division / Q000235:genetics; D005313:Fetal Death / Q000235:genetics; D018628:Gene Dosage; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics; D009420:Nervous System / Q000196:embryology*; D009436:Neural Tube Defects / Q000235:genetics* / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism
D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases