記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00125-021-05488-2

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Endocrinology (United States)  

Pancreatic islet inflammation plays a crucial role in the etiology of type 2 diabetes (T2D). Macrophages residing in pancreatic islets have emerged as key players in islet inflammation. Macrophages express a plethora of innate immune receptors that bind to environmental and metabolic cues and integrate these signals to trigger an inflammatory response that contributes to the development of islet inflammation. One such receptor, Dectin-2, has been identified within pancreatic islets; however, its role in glucose metabolism remains largely unknown. Here we have demonstrated that mice lacking Dectin-2 exhibit local inflammation within islets, along with impaired insulin secretion and β-cell dysfunction. Our findings indicate that these effects are mediated by proinflammatory cytokines, such as interleukin (IL)-1α and IL-6, which are secreted by macrophages that have acquired an inflammatory phenotype because of the loss of Dectin-2. This study provides novel insights into the mechanisms underlying the role of Dectin-2 in the development of islet inflammation.

DOI： 10.1210/endocr/bqad181

Web of Science

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

The Cre-loxP strategy for tissue-specific gene inactivation has become a widely employed tool in several research studies. Conversely, inadequate breeding and genotyping without considering the potential for non-specific Cre-recombinase expression may lead to misinterpretations of results. Nestin-Cre transgenic mice, widely used for the selective deletion of genes in neurons, have been observed to have an incidence of Cre-line germline recombination. In this study, we attempted to generate neuron-specific Glucagon-like peptide 1 receptor (Glp1r) knock-out mice by crossing mice harboring the Nestin-Cre transgene with mice harboring the Glp1r gene modified with loxP insertion, in order to elucidate the role of Glp1r signaling in the nervous system. Surprisingly, during this breeding process, we discovered that the null allele emerged in the offspring irrespective of the presence or absence of the Nestin-Cre transgene, with a high probability of occurrence (93.6%). To elucidate the cause of this null allele, we conducted breeding experiments between mice carrying the heterozygous Glp1r null allele but lacking the Nestin-Cre transgene. We confirmed that the null allele was inherited by the offspring independently of the Nestin-Cre transgene. Furthermore, we assessed the gene expression, protein expression, and phenotype of mice carrying the homozygous Glp1r null allele generated from the aforementioned breeding, thereby confirming that the null allele indeed caused a global knock-out of Glp1r. These findings suggest that the null allele in the NestinCre-Glp1r floxed breeding arose due to germline recombination. Moreover, we demonstrated the possibility that germline recombination may occur not only during the spermatogenesis at testis but also during epididymal sperm maturation. The striking frequency of germline recombination in the Nestin-Cre driver underscores the necessity for caution when implementing precise breeding strategies and employing suitable genotyping methods.

DOI： 10.1371/journal.pone.0296006

Web of Science

Scopus

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当ページ：第68巻5号, pp.644-651   記述言語：日本語   著書種別：学術書

担当ページ：第101巻, 第2号, pp.142-147   記述言語：日本語   著書種別：学術書

担当ページ：pp.154   記述言語：日本語   著書種別：学術書

担当ページ：第92巻1号、pp.9-14   記述言語：日本語   著書種別：学術書

担当ページ：第39巻、第3号（2022年5・6月号）pp.284-291   記述言語：日本語   著書種別：学術書

開催年月日： 2024年3月

記述言語：日本語  

開催地：佐賀県医療センター好生館（久留米市）   国名：日本国  

開催年月日： 2023年12月

記述言語：日本語  

開催地：熊本大学（熊本市）   国名：日本国  

開催年月日： 2023年12月

記述言語：日本語  

開催地：熊本大学（熊本市）   国名：日本国  

開催年月日： 2023年11月

記述言語：日本語  

開催地：東北大学/岩手医科大学（仙台市）   国名：日本国  

開催年月日： 2023年11月

記述言語：日本語  

開催地：東北大学/岩手医科大学（仙台市）   国名：日本国  

種別：大会・シンポジウム等 

種別：大会・シンポジウム等