scholarly journals Common Laboratory Mice Are Susceptible to Infection with the SARS-CoV-2 Beta Variant

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2263
Author(s):  
Ravi Kant ◽  
Lauri Kareinen ◽  
Teemu Smura ◽  
Tobias L. Freitag ◽  
Sawan Kumar Jha ◽  
...  
Keyword(s):  
Small Animal ◽  
Murine Models ◽  
Laboratory Mice ◽  
Wild Type ◽  
Naturally Occurring ◽  
Virus Dose ◽  
Pulmonary Changes ◽  
Small Animal Models ◽  
Virus Strains ◽  
Common Laboratory

Small animal models are of crucial importance for assessing COVID-19 countermeasures. Common laboratory mice would be well-suited for this purpose but are not susceptible to infection with wild-type SARS-CoV-2. However, the development of mouse-adapted virus strains has revealed key mutations in the SARS-CoV-2 spike protein that increase infectivity, and interestingly, many of these mutations are also present in naturally occurring SARS-CoV-2 variants of concern. This suggests that these variants might have the ability to infect common laboratory mice. Herein we show that the SARS-CoV-2 beta variant attains infectibility to BALB/c mice and causes pulmonary changes within 2–3 days post infection, consistent with results seen in other murine models of COVID-19, at a reasonable virus dose (2 × 105 PFU). The findings suggest that common laboratory mice can serve as the animal model of choice for testing the effectiveness of antiviral drugs and vaccines against SARS-CoV-2.

scholarly journals Common laboratory mice are susceptible to infection with SARS-CoV2 beta variant

2021 ◽  
Author(s):  
Ravi Kant ◽  
Lauri Kareinen ◽  
Teemu Smura ◽  
Tobias L. Freitag ◽  
Sawan Kumar Jha ◽  
...  
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
Laboratory Mice ◽  
Crucial Importance ◽  
Wild Type ◽  
Pulmonary Changes ◽  
Small Animal Models ◽  
Common Laboratory

Abstract Small animal models are of crucial importance for assessing COVID-19 countermeasures. Common laboratory mice would be well-suited for this purpose but are not susceptible to infection with wild-type SARS-CoV-2. Herein we show that the SARS-CoV-2 beta variant attains infectibility to BALB/c mice and causes pulmonary changes consistent with COVID-19.

scholarly journals History of IgA Nephropathy Mouse Models

2021 ◽  
Vol 10 (14) ◽  
pp. 3142
Author(s):  
Batoul Wehbi ◽  
Virginie Pascal ◽  
Lina Zawil ◽  
Michel Cogné ◽  
Jean-Claude Aldigier
Keyword(s):  
Iga Nephropathy ◽  
Small Animal ◽  
Experimental Models ◽  
Murine Models ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Simple Description ◽  
Primary Glomerulonephritis ◽  
History Of ◽  
Small Animal Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

scholarly journals The Representative Porcine Model for Human Cardiovascular Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yoriyasu Suzuki ◽  
Alan C. Yeung ◽  
Fumiaki Ikeno
Keyword(s):  
Animal Models ◽  
Porcine Model ◽  
Small Animal ◽  
Large Animal ◽  
Murine Models ◽  
Practical Applications ◽  
Large Animal Models ◽  
Small Animal Models ◽  
Insight Into

To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions. This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.

scholarly journals Assessment of Environmental and Occupational Exposure while Working with Candida auris a Multidrug Resistant (MDR) Fungus in the Animal Facility.

2018 ◽  
Author(s):  
Steven R. Torres ◽  
Heather C. Kim ◽  
Lynn Leach ◽  
Sudha Chaturvedi ◽  
Corey J. Bennett ◽  
...  
Keyword(s):  
Occupational Exposure ◽  
Animal Models ◽  
Fungal Pathogen ◽  
Small Animal ◽  
Multidrug Resistant ◽  
Murine Models ◽  
Candida Auris ◽  
Buddy System ◽  
Small Animal Models ◽  
Dose Dependent

In less than a decade since its identification in 2009, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality. Unlike any other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models use inoculums as high as 107-108 cells per mouse, and the environmental and occupational exposure of working with these models has not been clearly defined. Using an intravenous model of C. auris infection, this study determined that shedding of the organism is dose-dependent. C. auris was detected in the cage bedding when mice were infected with 107 and 108 cells, but not with doses of 105 and 106 cells. Potential for exposure to C. auris during necropsies and when working with infected tissues was also demonstrated. To mitigate these potential exposures, a rigorous buddy system workflow, biomonitoring and disinfection procedures were developed that can be used to prevent accidental exposures when using small animal models of C. auris infection.

scholarly journals The Mx1 Gene Protects Mice against the Pandemic 1918 and Highly Lethal Human H5N1 Influenza Viruses

2007 ◽  
Vol 81 (19) ◽  
pp. 10818-10821 ◽  
Author(s):  
Terrence M. Tumpey ◽  
Kristy J. Szretter ◽  
Neal Van Hoeven ◽  
Jacqueline M. Katz ◽  
Georg Kochs ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
Innate Immune ◽  
Laboratory Mice ◽  
Wild Type ◽  
H5n1 Influenza ◽  
Mx1 Gene ◽  
1918 Influenza ◽  
Human H5n1 ◽  
Common Laboratory

ABSTRACT Mice carrying a wild-type Mx1 gene (Mx1 +/+ ) differ from standard laboratory mice (Mx1 −/−) in being highly resistant to infection with common laboratory strains of influenza A virus. We report that Mx1 also protects mice against the pandemic human 1918 influenza virus and a highly lethal human H5N1 strain from Vietnam. Resistance to H5N1 of Mx1 +/+ but not Mx1 −/− mice was enhanced if the animals were treated with a single dose of exogenous alpha interferon before infection. Thus, the interferon-induced resistance factor Mx1 represents a key component of the murine innate immune system that mediates protection against epidemic and pandemic influenza viruses.

Evaluation of flow-cytometry for the monitoring of infectious human rotavirus in water

1997 ◽  
Vol 35 (11-12) ◽  
pp. 451-453
Author(s):  
F. X. Abad ◽  
A. Bosch ◽  
J. Comas ◽  
D. Villalba ◽  
R. M. Pintó
Keyword(s):  
Flow Cytometry ◽  
Water Samples ◽  
Wild Type ◽  
Cell Monolayers ◽  
Naturally Occurring ◽  
Human Rotavirus ◽  
Faecal Samples

A method has been developed for the detection of infectious human rotavirus (HRV), based on infection of MA104 and CaCo-2 cell monolayers and ulterior flow cytometry. The sensitivity of the flow cytometry procedure for the cell-adapted HRV enabled the detection of 200 and 2 MPNCU in MA104 and CaCo-2 cells, respectively. Flow cytometry performed five days after infection of CaCo-2 enabled the detection of naturally occurring wild-type HRV in faecal samples and concentrated water samples.

scholarly journals Rationally repurposed nitroxoline inhibits preclinical models of Epstein–Barr virus-associated lymphoproliferation

2021 ◽  
Author(s):  
Maite Ibáñez de Garayo ◽  
Wendi Liu ◽  
Nicole C. Rondeau ◽  
Christopher B. Damoci ◽  
JJ L. Miranda
Keyword(s):  
Epstein Barr Virus ◽  
Small Animal ◽  
Preclinical Models ◽  
Bet Inhibitor ◽  
Barr Virus ◽  
Chelating Activity ◽  
Metal Chelating ◽  
Small Animal Models ◽  
Epstein Barr ◽  
Tract Infections

AbstractRepurposing of currently used drugs for new indications benefits from known experience with those agents. Rational repurposing can be achieved when newly uncovered molecular activities are leveraged against diseases that utilize those mechanisms. Nitroxoline is an antibiotic with metal-chelating activity used to treat urinary tract infections. This small molecule also inhibits the function of bromodomain and extraterminal (BET) proteins that regulate oncogene expression in cancer. Lymphoproliferation driven by the Epstein–Barr virus (EBV) depends on these same proteins. We therefore tested the efficacy of nitroxoline against cell culture and small animal models of EBV-associated lymphoproliferation. Nitroxoline indeed reduces cell and tumor growth. Nitroxoline also acts faster than the prototype BET inhibitor JQ1. We suggest that this rational repurposing may hold translational promise.

scholarly journals Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1637
Author(s):  
Solida Long ◽  
Joana B. Loureiro ◽  
Carla Carvalho ◽  
Luís Gales ◽  
Lucília Saraiva ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Small Molecules ◽  
Tumor Cells ◽  
Mutant P53 ◽  
Wild Type ◽  
Naturally Occurring ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Amino Derivatives ◽  
Carbazole Alkaloids

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.

scholarly journals Responsiveness to exogenous cAMP of a Saccharomyces cerevisiae strain conferred by naturally occurring alleles of PDE1 and PDE2.

Genetics ◽  
1993 ◽  
Vol 135 (2) ◽  
pp. 321-326 ◽  
Author(s):  
H Mitsuzawa
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Slow Growth ◽  
Loss Of Function ◽  
Wild Type ◽  
Triple Mutant ◽  
Apparent Absence ◽  
Camp Pathway ◽  
Naturally Occurring ◽  
Elevated Activity ◽  
Growth Phenotype

Abstract The Saccharomyces cerevisiae strain P-28-24C, from which cAMP requiring mutants derived, responded to exogenously added cAMP. Upon the addition of cAMP, this strain showed phenotypes shared by mutants with elevated activity of the cAMP pathway. Genetic analysis involving serial crosses of this strain to a strain with another genetic background revealed that the responsiveness to cAMP results from naturally occurring loss-of-function alleles of PDE1 and PDE2, which encode low and high affinity cAMP phosphodiesterases, respectively. In addition, P-28-24C was found to carry a mutation conferring slow growth that lies in CYR1, which encodes adenylate cyclase, and the slow growth phenotype caused by the cyr1 mutation was suppressed by the pde2 mutation. Therefore P-28-24C is fortuitously a pde1 pde2 cyr1 triple mutant. Responsiveness to cAMP conferred by pde mutations suggests that S. cerevisiae cells are permeable to cAMP to some extent and that the apparent absence of effect of exogenously added cAMP on wild-type cells is due to immediate degradation by cAMP phosphodiesterases.

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