scholarly journals Interleukin-17 Receptor A1 Gene Knockout Causes Weight Loss and Reduction of Intestinal Metabolism-Related Genes in The Japanese Medaka, Oryzias Latipes

Author(s):  
Yo Okamura ◽  
Hiroshi Miyanishi ◽  
Masato Kinoshita ◽  
Tomoya Kono ◽  
Masahiro Sakai ◽  
...  

Abstract In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (RA1), an IL-17A/F receptor, in Japanese medaka (Oryzias latipes) using genome editing technique and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparing gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yo Okamura ◽  
Hiroshi Miyanishi ◽  
Masato Kinoshita ◽  
Tomoya Kono ◽  
Masahiro Sakai ◽  
...  

AbstractIn the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (IL-17RA1, an IL-17A/F receptor) in Japanese medaka (Oryzias latipes) using genome editing technique, and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparison of gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. Conversely, expression of genes related to cardiovascular system development, including fli1a, sox7, and notch1b in the anterior intestine, and that of genes related to oxidation–reduction processes including ugp2a, aoc1, and nos1 in posterior intestine was up-regulated in IL-17RA1-KO medaka. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.


2011 ◽  
Vol 30 (4-5) ◽  
pp. 1131-1137 ◽  
Author(s):  
Liwei Sun ◽  
Xiaolu Shao ◽  
Yudan Wu ◽  
Jingming Li ◽  
Qinfang Zhou ◽  
...  

2019 ◽  
Vol 20 (14) ◽  
pp. 3573 ◽  
Author(s):  
Zhenghua He ◽  
Jinfeng Wu ◽  
Xiaopeng Sun ◽  
Mingqiu Dai

As the core components of abscisic acid (ABA) signal pathway, Clade A PP2C (PP2C-A) phosphatases in ABA-dependent stress responses have been well studied in Arabidopsis. However, the roles and natural variations of maize PP2C-A in stress responses remain largely unknown. In this study, we investigated the expression patterns of ZmPP2C-As treated with multiple stresses and generated transgenic Arabidopsis plants overexpressing most of the ZmPP2C-A genes. The results showed that the expression of most ZmPP2C-As were dramatically induced by multiple stresses (drought, salt, and ABA), indicating that these genes may have important roles in response to these stresses. Compared with wild-type plants, ZmPP2C-A1, ZmPP2C-A2, and ZmPP2C-A6 overexpression plants had higher germination rates after ABA and NaCl treatments. ZmPP2C-A2 and ZmPP2C-A6 negatively regulated drought responses as the plants overexpressing these genes had lower survival rates, higher leaf water loss rates, and lower proline accumulation compared to wild type plants. The natural variations of ZmPP2C-As associated with drought tolerance were also analyzed and favorable alleles were detected. We widely studied the roles of ZmPP2C-A genes in stress responses and the natural variations detected in these genes have the potential to be used as molecular markers in genetic improvement of maize drought tolerance.


2010 ◽  
Vol 9 (1) ◽  
pp. 41-57 ◽  
Author(s):  
Kelly M. Pennington ◽  
Anne R. Kapuscinski ◽  
Michael S. Morton ◽  
Anne M. Cooper ◽  
Loren M. Miller

1998 ◽  
Vol 72 (7) ◽  
pp. 5797-5801 ◽  
Author(s):  
Andrea Knappe ◽  
Christian Hiller ◽  
Henk Niphuis ◽  
François Fossiez ◽  
Mathias Thurau ◽  
...  

ABSTRACT In comparison to wild-type herpesvirus saimiri, viral interleukin-17 gene knockout mutants have unaltered behavior regarding viral replication, T-cell transformation in vitro, and pathogenicity in cottontop tamarins. Thus, this gene is not required for T-cell lymphoma induction but may contribute to apathogenic viral persistence in the natural host, the squirrel monkey.


2019 ◽  
Author(s):  
Hua Chen ◽  
Lijuan Zhang ◽  
Suyi Li ◽  
Ling Ke ◽  
Chentao Lin ◽  
...  

AbstractVibrio vulnificus (V. vulnificus) is an aquatic pathogen that can cause primary sepsis and soft tissue infection. CpG oligodeoxynucleotides (CpG-ODN) are a type of essential immunomodulators, which can trigger or enhance immune responses in mammals, fish, and humans. In this study, we evaluated the effect of CpG-ODN 2007 as a potential immunostimulant for zebrafish infected with V. vulnificus (FJ03-X2). Fish injected with the CpG-ODN 2007 showed lower mortality rate compared with the fish that did not receive treatment. The survival rates of CpG-ODN 2007-treated group and PBS-treated group were 85% and 57.9%, respectively. In addition, our in vitro results demonstrated that CpG-ODN 2007 can effectively reduce the toxicity of V. vulnificus (FJ03-X2) to zebrafish embryonic fibroblast (ZF4) cells. Furthermore, we assessed immune-related genes expression patterns in FJ03-X2 infected zebrafish or ZF4 cells with and without CpG-ODN 2007 treatment, such as TLRs and IL-1β. To sum up, our data indicated that CpG-ODN 2007 protects zebrafish against Vibrio vulnificus induced infection.


2021 ◽  
Vol 22 (23) ◽  
pp. 12997
Author(s):  
Hideaki Nishie ◽  
Akiko Nakano-Doi ◽  
Toshinori Sawano ◽  
Takayuki Nakagomi

An accumulation of evidence shows that endogenous neural stem/progenitor cells (NSPCs) are activated following brain injury such as that suffered during ischemic stroke. To understand the expression patterns of these cells, researchers have developed mice that express an NSPC marker, Nestin, which is detectable by specific reporters such as green fluorescent protein (GFP), i.e., Nestin-GFP mice. However, the genetic background of most transgenic mice, including Nestin-GFP mice, comes from the C57BL/6 strain. Because mice from this background strain have many cerebral arterial branches and collateral vessels, they are accompanied by several major problems including variable ischemic areas and high mortality when subjected to ischemic stroke by occluding the middle cerebral artery (MCA). In contrast, CB-17 wild-type mice are free from these problems. Therefore, with the aim of overcoming the aforementioned defects, we first crossed Nestin-GFP mice (C57BL/6 background) with CB-17 wild-type mice and then developed Nestin-GFP mice (CB-17 background) by further backcrossing the generated hybrid mice with CB-17 wild-type mice. Subsequently, we investigated the phenotypes of the established Nestin-GFP mice (CB-17 background) following MCA occlusion; these mice had fewer blood vessels around the MCA compared with the number of blood vessels in Nestin-GFP mice (C57BL/6 background). In addition, TTC staining showed that infarcted volume was variable in Nestin-GFP mice (C57BL/6 background) but highly reproducible in Nestin-GFP mice (CB-17 background). In a further investigation of mice survival rates up to 28 days after MCA occlusion, all Nestin-GFP mice (CB-17 background) survived the period, whereas Nestin-GFP mice (C57BL/6 background) frequently died within 1 week and exhibited a higher mortality rate. Immunohistochemistry analysis of Nestin-GFP mice (CB-17 background) showed that GFP+ cells were mainly obverted in not only conventional neurogenic areas, including the subventricular zone (SVZ), but also ischemic areas. In vitro, cells isolated from the ischemic areas and the SVZ formed GFP+ neurosphere-like cell clusters that gave rise to various neural lineages including neurons, astrocytes, and oligodendrocytes. However, microarray analysis of these cells and genetic mapping experiments by Nestin-CreERT2 Line4 mice crossed with yellow fluorescent protein (YFP) reporter mice (Nestin promoter-driven YFP-expressing mice) indicated that cells with NSPC activities in the ischemic areas and the SVZ had different characteristics and origins. These results show that the expression patterns and fate of GFP+ cells with NSPC activities can be precisely investigated over a long period in Nestin-GFP mice (CB-17 background), which is not necessarily possible with Nestin-GFP mice (C57BL/6 background). Thus, Nestin-GFP mice (CB-17 background) could become a useful tool with which to investigate the mechanism of neurogenesis via the aforementioned cells under pathological conditions such as following ischemic stroke.


Sign in / Sign up

Export Citation Format

Share Document