MKK7 deficiency in mature neurons impairs parental behavior in mice.

Tadashi Shin, Yuichi Hiraoka, Tokiwa Yamasaki, Jamey D Marth, Josef M Penninger, Masami Kanai-Azuma, Kohichi Tanaka, Satoshi Kofuji, Hiroshi Nishina

Genes to cells : devoted to molecular & cellular mechanisms 2021 Jan

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c-Jun N-terminal kinases (JNKs) are constitutively activated in mammalian brains and are indispensable for their development and neural functions. MKK7 is an upstream activator of all JNKs. However, whether the common JNK signaling pathway regulates the brain's control of social behavior remains unclear. Here, we show that female mice in which Mkk7 is deleted specifically in mature neurons (Mkk7flox/flox Syn-Cre mice) give birth to a normal number of pups but fail to raise them due to a defect in pup retrieval. To explore the mechanism underlying this abnormality, we performed comprehensive behavioral tests. Mkk7flox/flox Syn-Cre mice showed normal locomotor functions and cognitive ability but exhibited depression-like behavior. cDNA microarray analysis of mutant brain revealed an altered gene expression pattern. Quantitative RT-PCR analysis demonstrated that mRNA expression levels of genes related to neural signaling pathways and a calcium channel were significantly different from controls. In addition, loss of neural MKK7 had unexpected regulatory effects on gene expression patterns in oligodendrocytes. These findings indicate that MKK7 has an important role in regulating the gene expression patterns responsible for promoting normal social behavior and staving off depression. © 2020 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Citation

Tadashi Shin, Yuichi Hiraoka, Tokiwa Yamasaki, Jamey D Marth, Josef M Penninger, Masami Kanai-Azuma, Kohichi Tanaka, Satoshi Kofuji, Hiroshi Nishina. MKK7 deficiency in mature neurons impairs parental behavior in mice. Genes to cells : devoted to molecular & cellular mechanisms. 2021 Jan;26(1):5-17