Targeted inactivation of Mapk4 in mice reveals specific nonredundant functions of Erk3/Erk4 subfamily mitogen-activated protein kinases
| Autor: | Sylvain Meloche, Erika Vigneault, Jean-François Poirier-Héon, Naguib Mechawar, Adeline Rachalski, Paul Déléris, Nicolas Cermakian, Benjamin Turgeon, Sonia Klinger, Justine Rousseau, Salah El Mestikawy, Maria Antonietta Davoli |
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| Rok vydání: | 2010 |
| Předmět: |
Subfamily
Genotype Neurogenesis Neuropsychological Tests Isozyme Mice Animals Tissue Distribution Molecular Biology Gene Cells Cultured Mitogen-Activated Protein Kinase 7 Mitogen-Activated Protein Kinase 6 Mice Knockout biology Behavior Animal Kinase Cell Biology Articles Fibroblasts Embryo Mammalian Phenotype Molecular biology Cell biology Isoenzymes Mitogen-activated protein kinase biology.protein Function (biology) |
| Zdroj: | Molecular and cellular biology. 30(24) |
| ISSN: | 1098-5549 |
| Popis: | Erk4 and Erk3 are atypical members of the mitogen-activated protein (MAP) kinase family. The high sequence identity of Erk4 and Erk3 proteins and the similar organization of their genes imply that the two protein kinases are paralogs. Recently, we have shown that Erk3 function is essential for neonatal survival and critical for the establishment of fetal growth potential and pulmonary function. To investigate the specific functions of Erk4, we have generated mice with a targeted disruption of the Mapk4 gene. We show that Erk4-deficient mice are viable and fertile and exhibit no gross morphological or physiological anomalies. Loss of Erk4 is not compensated by changes in Erk3 expression or activity during embryogenesis or in adult tissues. We further demonstrate that additional loss of Erk4 does not exacerbate the fetal growth restriction and pulmonary immaturity phenotypes of Erk3(-/-) mice and does not compromise the viability of Erk3(+/-) neonates. Interestingly, behavioral phenotyping revealed that Erk4-deficient mice manifest depression-like behavior in the forced-swimming test. Our analysis indicates that the MAP kinase Erk4 is dispensable for mouse embryonic development and reveals that Erk3 and Erk4 have acquired specialized functions through evolutionary diversification. |
| Databáze: | OpenAIRE |
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