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MKK7 deficiency in mature neurons impairs parental behavior in mice
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 remain...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839552/ https://www.ncbi.nlm.nih.gov/pubmed/33098150 http://dx.doi.org/10.1111/gtc.12816 |
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author | Shin, Tadashi Hiraoka, Yuichi Yamasaki, Tokiwa Marth, Jamey D. Penninger, Josef M. Kanai‐Azuma, Masami Tanaka, Kohichi Kofuji, Satoshi Nishina, Hiroshi |
author_facet | Shin, Tadashi Hiraoka, Yuichi Yamasaki, Tokiwa Marth, Jamey D. Penninger, Josef M. Kanai‐Azuma, Masami Tanaka, Kohichi Kofuji, Satoshi Nishina, Hiroshi |
author_sort | Shin, Tadashi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7839552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78395522021-02-01 MKK7 deficiency in mature neurons impairs parental behavior in mice Shin, Tadashi Hiraoka, Yuichi Yamasaki, Tokiwa Marth, Jamey D. Penninger, Josef M. Kanai‐Azuma, Masami Tanaka, Kohichi Kofuji, Satoshi Nishina, Hiroshi Genes Cells Original Articles 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. John Wiley and Sons Inc. 2020-11-18 2021-01 /pmc/articles/PMC7839552/ /pubmed/33098150 http://dx.doi.org/10.1111/gtc.12816 Text en © 2020 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Shin, Tadashi Hiraoka, Yuichi Yamasaki, Tokiwa Marth, Jamey D. Penninger, Josef M. Kanai‐Azuma, Masami Tanaka, Kohichi Kofuji, Satoshi Nishina, Hiroshi MKK7 deficiency in mature neurons impairs parental behavior in mice |
title | MKK7 deficiency in mature neurons impairs parental behavior in mice |
title_full | MKK7 deficiency in mature neurons impairs parental behavior in mice |
title_fullStr | MKK7 deficiency in mature neurons impairs parental behavior in mice |
title_full_unstemmed | MKK7 deficiency in mature neurons impairs parental behavior in mice |
title_short | MKK7 deficiency in mature neurons impairs parental behavior in mice |
title_sort | mkk7 deficiency in mature neurons impairs parental behavior in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839552/ https://www.ncbi.nlm.nih.gov/pubmed/33098150 http://dx.doi.org/10.1111/gtc.12816 |
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