Journal
GENES TO CELLS
Volume 26, Issue 1, Pages 5-17Publisher
WILEY
DOI: 10.1111/gtc.12816
Keywords
JNK; mature neuron; MKK7; parental behavior
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [JP17H03982, JP20H03381]
- Tokyo Medical and Dental University (TMDU)
- AMED [JP18fk0210042, JP19fk0210042, JP20fk02100, 42]
- NIH [DK048247]
- [JP17H05996]
- [JP19H04953]
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Deletion of Mkk7 specifically in mature neurons in female mice leads to a defect in pup retrieval despite normal birth rates, indicating an important role of MKK7 in regulating gene expression patterns for normal social behavior and depression prevention. The mutant mice also exhibit depression-like behavior and alterations in gene expression related to neural signaling pathways and a calcium channel. Loss of neural MKK7 unexpectedly affects gene expression patterns in oligodendrocytes.
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 (Mkk7(flox/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. Mkk7(flox/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.
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