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In vivo functions of mitogen-activated protein kinases: conclusions from knock-in and knock-out mice

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Abstract

Multicellular organisms achieve intercellular communication by means of signalling molecules whose effect on the target cell is mediated by signal transduction pathways. Such pathways relay, amplify and integrate signals to elicit appropriate biological responses. Protein kinases form crucial intermediate components of numerous signalling pathways. One group of protein kinases, the mitogen-activated protein kinases (MAP kinases) are kinases involved in signalling pathways that respond primarily to mitogens and stress stimuli. In vitro studies revealed that the MAP kinases are implicated in several cellular processes, including cell division, differentiation, cell survival/apoptosis, gene expression, motility and metabolism. As such, dysfunction of specific MAP kinases is associated with diseases such as cancer and immunological disorders. However, the genuine in vivo functions of many MAP kinases remain elusive. Genetically modified mouse models deficient in a specific MAP kinase or expressing a constitutive active or a dominant negative variant of a particular MAP kinase offer valuable tools for elucidating the biological role of these protein kinases. In this review, we focus on the current status of MAP kinase knock-in and knock-out mouse models and their phenotypes. Moreover, examples of the application of MAP kinase transgenic mice for validating therapeutic properties of specific MAP kinase inhibitors, and for investigating the role of MAP kinase in pathogen-host interactions will be discussed.

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Abbreviations

ASO’s:

antisense oligonucleotides

ca:

constitutive active

dn:

dominant negative

KI:

knock-in

KO:

knock-out

LV:

left ventricular

MAP kinase:

mitogen activated protein kinase

MAPKK:

mitogen activated protein kinase kinase

MAPKKK:

mitogen activated protein kinase kinase kinase

MAPKAPK:

mitogen activated protein kinase-activated protein kinase

MMP:

matrix metalloproteinase

NTG:

non-transgenic

TAC:

transverse aortic constriction

TG:

transgenic

VILI:

ventilator induced lung injury

WT:

wild-type

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Gerits, N., Kostenko, S. & Moens, U. In vivo functions of mitogen-activated protein kinases: conclusions from knock-in and knock-out mice. Transgenic Res 16, 281–314 (2007). https://doi.org/10.1007/s11248-006-9052-0

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