scholarly journals The Optimal Condition of Poly(I: C)-Induced Knockout of Cre Recombinase for Mx1-Cre/ Cre-loxP Mice

2021 ◽  
Author(s):  
Bijie Yang ◽  
Haobiao Wang ◽  
Yuanyuan Liu ◽  
Feifei Xiao ◽  
Mei Kuang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Knockout Mice ◽  
Low Dose ◽  
Gene Knockout ◽  
Conditional Knockout ◽  
Poly I:C ◽  
High Dose ◽  
P System ◽  
Single High Dose ◽  
Pure Poly

Abstract BackgroundThe Cre-loxP system is widely applied for conditional knockout mice, commonly used to study the function of specific genes. Although some different promoters drive Cre expression, the poly(I: C)-inducible Mx1-Cre is the most commonly used to delete the target gene in experimental hematology. However, the optimal induction knockout condition for Mx1-Cre/ Cre-loxP mice using the Poly(I:C)-inducible Cre-loxP conditional system remains unclear. Here, we present two different components and three injection protocols of poly(I: C) to find the optimized condition. ResultsThe results showed that the better knockout efficiency of Cre-loxP in mice injected with pure poly(I: C) has than those injected with poly(I: C) with some components. From the perspective of lethal genes (Brg1), data showed that mice injected with a single high dose (500 µg) of pure Poly (I:C) had a lower knockout rate. For mice injected media-dose (10µg/g) poly(I: C) triple, which induced a high knockout rate, but the mortality rate was still high. Importantly, the mice injected low-dose (6µg/g) poly(I: C) triple, both the knockout rate and survival rate of mice was high. Similarly, the knockout rate of non-lethal mice injected with media-dose (10µg/g) or low-dose (6μg/g) poly(I: C) triple was very high, but injected with a single high dose (500 µg) of pure poly(I: C) had a low knockout rate. ConclusionOur studies provided the optimized condition for using poly(I: C)-inducible effective knockout and maintaining the survival rate for the Cre-loxP mice, which might be applied in other knockout mice for this system to ensure both the gene knockout and the mice survival.

scholarly journals Advantages of Repeated Low Dose against Single High Dose of Kainate in C57BL/6J Mouse Model of Status Epilepticus: Behavioral and Electroencephalographic Studies

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96622 ◽  
Author(s):  
Karen Tse ◽  
Sreekanth Puttachary ◽  
Edward Beamer ◽  
Graeme J. Sills ◽  
Thimmasettappa Thippeswamy
Keyword(s):  
Status Epilepticus ◽  
Mouse Model ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose

Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice

1997 ◽  
Vol 272 (2) ◽  
pp. R563-R569 ◽  
Author(s):  
L. R. Leon ◽  
W. Kozak ◽  
J. Peschon ◽  
M. J. Kluger
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Motor Activity ◽  
Knockout Mice ◽  
Low Dose ◽  
Late Phase ◽  
High Dose ◽  
Wild Type ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.

Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide

2000 ◽  
Vol 77 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Gianpaolo Papaccio ◽  
Francesco Aurelio Pisanti ◽  
Michael V.G. Latronico ◽  
Eduardo Ammendola ◽  
Michela Galdieri
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose

scholarly journals The effects of single high dose vs daily low dose oral cholecalciferol treatment on vitamin D levels and muscle strenght in posmenapousal women

2015 ◽  
Author(s):  
Mahmut Apaydin ◽  
Asli Gencay Can ◽  
Seyfullah Kan ◽  
Selvihan Beysel ◽  
Taner Demirci ◽  
...  
Keyword(s):  
Vitamin D ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose ◽  
Vitamin D Levels ◽  
Dose Oral

scholarly journals Kaempferol Protects Mice from D-GalN/LPS-induced Acute Liver Failure by Regulating the Autophagy Pathway

2020 ◽  
Author(s):  
Yuan Tian ◽  
Feng Ren ◽  
Ling Xu ◽  
Weihua Li ◽  
Mei Liu ◽  
...  
Keyword(s):  
Survival Rate ◽  
Liver Function ◽  
Opposite Effect ◽  
Low Dose ◽  
High Dose ◽  
Severe Liver ◽  
Autophagy Pathway ◽  
Different Doses

Abstract Background Kaempferol, a flavonoid compound present in many edible plants, has been used in traditional medicine and has various biological functions. Acute liver failure (ALF) is a lethal clinical syndrome with severe liver function damage. There are currently no effective treatments for ALF except for liver transplantation. The aim of this study is to explored the mechanisms underlying the therapeutic effect of kaempferol in ALF. Methods The ALF mouse model was established using D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 10 µg/kg). Two hours before the administration of D-GalN/LPS, different group of mice were pretreated according different doses of kaempferol, 6 hours after injection of D-GalN/LPS, and then killed. The survival rate, liver function and inflammatory cytokine levels were assessed. It was determined whether kaempferol pretreatment protected hepatocytes from ALF induced by D-GalN/LPS via autophagy pathway in vivo and in vitro. Results Pretreatment with a high dose of kaempferol significantly decreased the survival rate and increased severe liver damage; however, pretreatment with a low dose of kaempferol showed the opposite effect. Furthermore, pretreatment with a high dose of kaempferol augment the levels of proinflammatory cytokines and markers of the MAPK signaling pathway, while pretreatment with a low dose of kaempferol showed the opposite effect. In addition, pretreatment with a high dose of kaempferol decreased autophagy, but pretreatment with a low dose of kaempferol increased autophagy in vivo and in vitro. It was also proved that pretreatment with 3-methyadenine (3- MA) or Atg7 siRNA to inhibit autophagy partially negated the hepatoprotective effect of kaempferol (5 mg/kg) pretreatment in ALF mice induced by D-GalN/LPS. Conclusions Our findings demonstrate that effects of different doses of kaempferol on D-GalN/LPS-induced ALF is remarkably different by regulating the autophagy pathway. Therefore, we should consider selecting the optimal dose of kaempferol as a potential treatment method for patients with ALF.

scholarly journals Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a Model for Vaccine Evaluation

2015 ◽  
Vol 89 (15) ◽  
pp. 7841-7851 ◽  
Author(s):  
Yufeng Song ◽  
Xiang Wang ◽  
Hongbo Zhang ◽  
Xinying Tang ◽  
Min Li ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Low Dose ◽  
Severe Disease ◽  
Influenza Vaccines ◽  
High Dose ◽  
Single High Dose ◽  
Virus Challenge ◽  
Cell Responses

ABSTRACTInfluenza infection causes severe disease and death in humans. In traditional vaccine research and development, a single high-dose virus challenge of animals is used to evaluate vaccine efficacy. This type of challenge model may have limitations. In the present study, we developed a novel challenge model by infecting mice repeatedly in short intervals with low doses of influenza A virus. Our results show that compared to a single high-dose infection, mice that received repeated low-dose challenges showed earlier morbidity and mortality and more severe disease. They developed higher vial loads, more severe lung pathology, and greater inflammatory responses and generated only limited influenza A virus-specific B and T cell responses. A commercial trivalent influenza vaccine protected mice against a single high and lethal dose of influenza A virus but was ineffective against repeated low-dose virus challenges. Overall, our data show that the repeated low-dose influenza A virus infection mouse model is more stringent and may thus be more suitable to select for highly efficacious influenza vaccines.IMPORTANCEInfluenza epidemics and pandemics pose serious threats to public health. Animal models are crucial for evaluating the efficacy of influenza vaccines. Traditional models based on a single high-dose virus challenge may have limitations. Here, we describe a new mouse model based on repeated low-dose influenza A virus challenges given within a short period. Repeated low-dose challenges caused more severe disease in mice, associated with higher viral loads and increased lung inflammation and reduced influenza A virus-specific B and T cell responses. A commercial influenza vaccine that was shown to protect mice from high-dose challenge was ineffective against repeated low-dose challenges. Overall, our results show that the low-dose repeated-challenge model is more stringent and may therefore be better suited for preclinical vaccine efficacy studies.

Sign in / Sign up

Export Citation Format

Share Document