Stiftung Tierärztliche Hochschule Hannover (TiHo)

Germ line deletion reveals a nonessential role of atypical mitogen-activated protein kinase 6/extracellular signal-regulated kinase 3

Ronkina, N; Schuster-Gossler, K; Hansmann, Florian GND; Kunze-Schumacher, H.; Sandrock, I.; Yakovleva, T; Lafera, J.; Baumgärtner, Wolfgang GND; Krueger, A.; Prinz, I.; Gossler, A.; Kotlyarov, A.; Gaestel, M.

Mitogen-activated protein kinase 6/extracellular signal-regulated kinase 3 (MAPK6/ERK3) is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary dysfunction and by defects in function, activation, and positive selection of T cells. To study the role of ERK3 in vivo, we generated mice carrying a conditional Erk3 allele with exon 3 flanked by loxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-cre and a clear reduction of the protein kinase MK5 is detected, providing the first evidence for the existence of the ERK3/MK5 signaling complex in vivo In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile and do not display pulmonary hypoplasia, acute respiratory failure, abnormal T-cell development, reduction of thymocyte numbers, or altered T-cell selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality and lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin resistance cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal, suggesting redundant functions of both protein kinases.

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Ronkina, N., Schuster-Gossler, K., Hansmann, F., Kunze-Schumacher, H., Sandrock, I., Yakovleva, T., Lafera, J., Baumgärtner, W., Krueger, A., Prinz, I., Gossler, A., Kotlyarov, A., Gaestel, M., 2019. Germ line deletion reveals a nonessential role of atypical mitogen-activated protein kinase 6/extracellular signal-regulated kinase 3. Molecular and cellular biology 39. https://doi.org/10.1128/mcb.00516-18
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