Targeted inactivation of Mapk4 in mice reveals specific nonredundant functions of Erk3/Erk4 subfamily mitogen-activated protein kinases.
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.
Institut de Recherche en Immunologie et Cancérologie, Université de Montréal, Montreal, Quebec, Canada.
Justine
J
Rousseau
Sonia
S
Klinger
Adeline
A
Rachalski
Benjamin
B
Turgeon
Paul
P
Déléris
Erika
E
Vigneault
Jean-François
JF
Poirier-Héon
Maria Antonietta
MA
Davoli
Naguib
N
Mechawar
Salah
S
El Mestikawy
Nicolas
N
Cermakian
Sylvain
S
Meloche
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005838:Genotype; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D048053:Mitogen-Activated Protein Kinase 6 / Q000235:genetics / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009483:Neuropsychological Tests; D014018:Tissue Distribution
D007527:Isoenzymes; D048053:Mitogen-Activated Protein Kinase 6; D048054:Mitogen-Activated Protein Kinase 7