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

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.

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yoriyasu Suzuki ◽  
Alan C. Yeung ◽  
Fumiaki Ikeno

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.


2021 ◽  
Vol 10 (11) ◽  
pp. 2369
Author(s):  
Izabella Z. A. Pawluczyk ◽  
Haresh Selvaskandan ◽  
Jonathan Barratt

IgA nephropathy (IgAN) is the most commonly diagnosed primary glomerulonephritis worldwide. It is a slow progressing disease with approximately 30% of cases reaching end-stage kidney disease within 20 years of diagnosis. It is currently only diagnosed by an invasive biopsy and treatment options are limited. However, the current surge in interest in RNA interference is opening up new horizons for the use of this new technology in the field of IgAN management. A greater understanding of the fundamentals of RNA interference offers exciting possibilities both for biomarker discovery and, more importantly, for novel therapeutic approaches to target key pathogenic pathways in IgAN. This review aims to summarise the RNA interference literature in the context of microRNAs and their association with the multifaceted aspects of IgA nephropathy.


2018 ◽  
Author(s):  
Steven R. Torres ◽  
Heather C. Kim ◽  
Lynn Leach ◽  
Sudha Chaturvedi ◽  
Corey J. Bennett ◽  
...  

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.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 161 ◽  
Author(s):  
Kar Neng Lai ◽  
Joseph C.K. Leung ◽  
Sydney C.W. Tang

Since its first description in 1968, IgA nephropathy has remained the most common form of primary glomerulonephritis leading to chronic kidney disease in developed countries. The clinical progression varies, and consequent end-stage renal disease occurs in 30% to 40% of patients 20 to 30 years after the first clinical presentation. Current data implicate overproduction of aberrantly glycosylated IgA1 as being pivotal in the induction of renal injury. Effective and specific treatment is still lacking, and new therapeutic approaches will be developed after better understanding the disease pathogenesis.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2263
Author(s):  
Ravi Kant ◽  
Lauri Kareinen ◽  
Teemu Smura ◽  
Tobias L. Freitag ◽  
Sawan Kumar Jha ◽  
...  

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.


2018 ◽  
Vol 11 (1) ◽  
pp. e227382 ◽  
Author(s):  
Shinichi Miyazaki ◽  
Akiko Hattori ◽  
Yasumasa Kuno ◽  
Takuya Ikeda

Immunoglobulin (Ig)A nephropathy is the most common cause of primary glomerulonephritis worldwide. While IgA nephropathy has been associated with a variety of other diseases, pulmonary complications are extremely rare. A 58-year-old man presented with a 2-week history of fever and exertional dyspnoea. A chest imaging revealed bilateral consolidation predominantly in upper lungs. Laboratory findings showed elevated serum creatinine with proteinuria and haematuria. Flexible bronchoscopy revealed diffuse alveolar haemorrhage, and IgA nephropathy was confirmed on a renal biopsy. He received prednisone with good effect. This case highlights the need to consider IgA nephropathy in the differential diagnosis of pulmonary renal syndrome.


Author(s):  
Maite Ibáñez de Garayo ◽  
Wendi Liu ◽  
Nicole C. Rondeau ◽  
Christopher B. Damoci ◽  
JJ L. Miranda

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.


Author(s):  
Alan C. Jackson

ABSTRACT:Worldwide, human rabies is prevalent where there is endemic dog rabies, but the disease may present unexpectedly in critical care units when suggestive clinical features have passed. In North America transmission from bats is most common and there is often no history of a bat bite or even contact with bats. Laboratory diagnostic evaluation for rabies includes serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Rare patients have survived rabies, and most received rabies vaccine prior to the onset of illness. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (dubbed the "Milwaukee Protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. There have been many subsequent failures of similar therapeutic approaches. There is no scientific rationale for the use of therapeutic coma in human rabies. New approaches to treating human rabies need to be developed.


Sign in / Sign up

Export Citation Format

Share Document