Dietary fats modulate neuroinflammation in mucin 2 knock out mice model of spontaneous colitis

Background Meperidine proved to be more effective in treatment of shivering than equianalgesic doses of other opioids, especially pure mu-agonists. Further, meperidine has well known nonopioid actions including agonistic effects at alpha2-adrenoceptors in vitro. Accordingly, the authors investigated nonopioid receptor-mediated effects of meperidine on thermoregulation using a mice model of nonshivering thermogenesis. To differentiate conceivable alpha2-adrenoceptor subtype specific interactions the authors analyzed wild-type mice and knock-out mice with deletion of the alpha2A-, alpha2B-, or alpha2C-adrenoceptor. Methods Ten mice per group (n = 60) were injected with saline, meperidine (20 mg/kg), saline plus naloxone (125 microg/kg), meperidine plus naloxone, fentanyl (50 microg/kg) plus naloxone, or meperidine plus atipamezole (2 mg/kg) intraperitoneally. Each mouse was subjected to the six different treatments. Then they were positioned into a plexiglas chamber where rectal temperature and mixed expired carbon dioxide were measured while whole body cooling was performed. Maximum response intensity and thermoregulatory threshold temperature of nonshivering thermogenesis were analyzed. Results Meperidine decreased the thermoregulatory threshold temperature in wild-type mice and alpha2B- and alpha2C-adrenoceptor knock-out mice. This effect ended after injection of the alpha2-adrenoceptor antagonist atipamezole. In wild-type and alpha2B-adrenoceptor knock-out mice, the decrease of thermoregulatory threshold was not reversible by administration of the opioid receptor antagonist naloxone. In contrast, in alpha2A-adrenoceptor knock-out mice, no decline of thermoregulatory threshold following meperidine injection was detectable. Maximum response intensity of nonshivering thermogenesis was comparable in all groups. Conclusions The authors' results suggest a major role of alpha2-adrenoceptors, especially the alpha2A subtype, in the mediation of thermoregulatory effects caused by meperidine in mice.

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In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.737912 ◽

2021 ◽

Vol 8 ◽

Author(s):

Nicola Bernabò ◽

Chiara Di Berardino ◽

Giulia Capacchietti ◽

Alessia Peserico ◽

Giorgia Buoncuore ◽

...

Keyword(s):

Theory Approach ◽

Mice Model ◽

Paracrine Factors ◽

Knock Out ◽

Network Nodes ◽

Scale Free ◽

Free Network ◽

Knock Out Mice ◽

Sensor Molecules

In vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been achieved,in medium-sized mammals, ivF has not been validated yet. Thus, the employment of a network theory approach has been proposed for interpreting the large amount of ivF information collected to date in different mammalian models in order to identify the controllers of the in vitro system. The WoS-derived data generated a scale-free network, easily navigable including 641 nodes and 2089 links. A limited number of controllers (7.2%) are responsible for network robustness by preserving it against random damage. The network nodes were stratified in a coherent biological manner on three layers: the input was composed of systemic hormones and somatic-oocyte paracrine factors; the intermediate one recognized mainly key signaling molecules such as PI3K, KL, JAK-STAT, SMAD4, and cAMP; and the output layer molecules were related to functional ivF endpoints such as the FSH receptor and steroidogenesis. Notably, the phenotypes of knock-out mice previously developed for hub.BN indirectly corroborate their biological relevance in early folliculogenesis. Finally, taking advantage of the STRING analysis approach, further controllers belonging to the metabolic axis backbone were identified, such as mTOR/FOXO, FOXO3/SIRT1, and VEGF, which have been poorly considered in ivF to date. Overall, this in silico study identifies new metabolic sensor molecules controlling ivF serving as a basis for designing innovative diagnostic and treatment methods to preserve female fertility.

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A Pig-a conditional knock-out mice model mediated by Vav-iCre: stable GPI-deficient and mild hemolysis

Experimental Hematology and Oncology ◽

10.1186/s40164-022-00254-5 ◽

2022 ◽

Vol 11 (1) ◽

Author(s):

Yingying Chen ◽

Hui Liu ◽

Lijie Zeng ◽

Liyan Li ◽

Dan Lu ◽

...

Keyword(s):

Stem Cells ◽

Animal Model ◽

Mouse Model ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Basic Research ◽

Mice Model ◽

Hematopoietic Stem ◽

Knock Out ◽

Knock Out Mice

AbstractParoxysmal nocturnal hemoglobinuria is a clonal disease caused by PIG-A mutation of hematopoietic stem cells. At present, there is no suitable PNH animal model for basic research, therefore, it is urgent to establish a stable animal model. We constructed a Pig-a conditional knock-out mice model by ES targeting technique and Vav-iCre. The expressions of GPI and GPI-AP were almost completely absent in CKO homozygote mice, and the proportion of the deficiency remained stable from birth. In CKO heterozygote mice, the proportion of the deficiency of GPI and GPI-AP was partially absent and decreased gradually from birth until it reached a stable level at 3 months after birth and remained there for life. Compared with normal C57BL/6N mice and Flox mice, pancytopenia was found in CKO homozygous mice, and leukopenia and anemia were found in CKO heterozygotes mice. Meanwhile, in CKO mice, the serum LDH, TBIL, IBIL, complement C5b-9 levels were increased, and the concentration of plasma FHb was increased. Hemosiderin granulosa cells can be seen more easily in the spleens of CKO mice. What’s more, CKO mice had stable transcription characteristics. In conclusion, our mouse model has stable GPI-deficient and mild hemolysis, which may be an ideal in vivo experimental model for PNH.

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Schistosoma Japonicum infection in Treg-specific USP21 knock-out mice

10.1101/2020.03.09.983502 ◽

2020 ◽

Author(s):

Youxiang Zhang ◽

Guina Xu ◽

Baoxin Zhang ◽

Shan Zhang ◽

Yangyang Li ◽

...

Keyword(s):

T Cells ◽

Schistosoma Japonicum ◽

Treg Cells ◽

Immune Homeostasis ◽

Mice Model ◽

Knock Out ◽

Specific Protease ◽

Knock Out Mice ◽

And Control ◽

Further Development

AbstractUSP21, an E3 de-ubiquitin enzyme playing vital roles in physiological activities, is important for Treg cells to maintain immune homeostasis and control immune tolerance. To understand its diverse functions and potential mechanism is essential for disease development. We, using the USP21 gene-conditional knock-out mice model of Schistosoma Japonicum infection, found more cercariae developed into adults, and more eggs deposited in the liver in KO mice. However, immunohistochemistry showed the degree and the area of egg granuloma and liver fibrosis were both reduced. This suggested knock-out USP21 did affect the immunoregulation between schistosomes and the host. In KO mice the content of IFN-gamma and IL-4, and the expression of anti-SEA IgG and anti-SWAP IgG both increased in the liver, spleen and blood by flow cytometry, while the content of IL-10, lL-17A, IL-23, IL-9 and the expression of USP21 and anti-SEA IgM decreased. This indicated USP21-knockout-Tregs promoted both Th1-type and Th2-type immunity and inhibited other immunities during schistosomes infection, which disordered the host immunity. This study revealed the immunomodulatory of USP21 and preliminarily suggests it might be essential to regulate the complex immune network between the host and schistosomes. USP21 provides a new possible target for schistosomiasis treatment in the future.Author summarySchistosomiasis is a common neglected tropical disease that affects more than 230 million people worldwide. Therefore, the study on the mechanism of immune interaction between schistosomas and the host is not only helpful for the understanding of immune homeostasis, but also helpful for the further development of the treatment of schistosomiasis. Ubiquitin Specific Protease 21(USP21) has been shown to be involved in the regulation of many biological processes, such as maintaining immune homeostasis and regulating cell growth. Here, we observed that the specific deletion of USP21 led to the decrease of mice’s ability to resist schistosomes infection and promoted the survival of schistosomes. It was also proved that unstable regulatory T cells would produce polarization phenomenon and promote differentiation to helper T cells, which would lead to disorder of immune response in mice. However, this process reduced the serious immune pathological damage caused by egg granuloma. Our findings reveal that USP21 may be an important molecule regulating immune interaction between Schistosoma japonicum and the host.

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High fat diet containing cholesterol induce aortic aneurysm through recruitment and proliferation of circulating agranulocytes in apoE knock out mice model

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-010-0446-8 ◽

2010 ◽

Vol 30 (2) ◽

pp. 154-163 ◽

Cited By ~ 24

Author(s):

K. Gopal ◽

Kishor Kumar ◽

R. Nandini ◽

P. Jahan ◽

M. J. Mahesh Kumar

Keyword(s):

Aortic Aneurysm ◽

High Fat Diet ◽

Mice Model ◽

High Fat ◽

Knock Out ◽

Knock Out Mice

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INFLUENCE OF COMPLEMENT SYSTEM ON POSTOPERATIVE PERITONITIS AND SEPSIS IN A KNOCK-OUT-MICE-MODEL

Shock ◽

10.1097/00024382-200106001-00105 ◽

2001 ◽

Vol 15 (Supplement) ◽

pp. 35

Author(s):

I. Celik ◽

C. Stover ◽

M. Botto ◽

M. Walport ◽

W. Schwaeble ◽

...

Keyword(s):

Complement System ◽

Postoperative Peritonitis ◽

Mice Model ◽

Knock Out ◽

Knock Out Mice

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Colonizing Microbes, IL-10 and IL-22: Keeping the Peace at the Mucosal Surface

Frontiers in Microbiology ◽

10.3389/fmicb.2021.729053 ◽

2021 ◽

Vol 12 ◽

Author(s):

Evelien Kidess ◽

Michiel Kleerebezem ◽

Sylvia Brugman

Keyword(s):

Host Immunity ◽

Mucosal Surface ◽

Microbial Colonization ◽

Developmental Phase ◽

Mice Model ◽

Host Genotype ◽

Microbial Composition ◽

Microbial World ◽

Knock Out ◽

Knock Out Mice

Our world is filled with microbes. Each multicellular organism has developed ways to interact with this microbial environment. Microbes do not always pose a threat; they can contribute to many processes that benefit the host. Upon colonization both host and microbes adapt resulting in dynamic ecosystems in different host niches. Regulatory processes develop within the host to prevent overt inflammation to beneficial microbes, yet keeping the possibility to respond when pathogens attempt to adhere and invade tissues. This review will focus on microbial colonization and the early (innate) host immune response, with special emphasis on the microbiota-modifying roles of IL-10 and IL-22 in the intestine. IL-10 knock out mice show an altered microbial composition, and spontaneously develop enterocolitis over time. IL-22 knock out mice, although not developing enterocolitis spontaneously, also have an altered microbial composition and increase of epithelial-adherent bacteria, mainly caused by a decrease in mucin and anti-microbial peptide production. Recently interesting links have been found between the IL-10 and IL-22 pathways. While IL-22 can function as a regulatory cytokine at the mucosal surface, it also has inflammatory roles depending on the context. For example, lack of IL-22 in the IL-10–/– mice model prevents spontaneous colitis development. Additionally, the reduced microbial diversity observed in IL-10–/– mice was also reversed in IL-10/IL-22 double mutant mice (Gunasekera et al., 2020). Since in early life, host immunity develops in parallel and in interaction with colonizing microbes, there is a need for future studies that focus on the effect of the timing of colonization in relation to the developmental phase of the host. To illustrate this, examples from zebrafish research will be compared with studies performed in mammals. Since zebrafish develop from eggs and are directly exposed to the outside microbial world, timing of the development of host immunity and subsequent control of microbial composition, is different from mammals that develop in utero and only get exposed after birth. Likewise, colonization studies using adult germfree mice might yield different results from those using neonatal germfree mice. Lastly, special emphasis will be given to the need for host genotype and environmental (co-housing) control of experiments.

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