The mouse model of oxygen-induced retinopathy: A suitable animal model for angiogenesis research

The lack of availability of a suitable animal model has limited understanding of the pathophysiology of meningococcal disease. We have utilized a neonatal mouse model in which atraumatic intranasal inoculation of meningococci results in nasopharyngeal colonization and ultimately bacteremia. Using this model, we compared the virulence of seven encapsulated meningococcal carrier strains with eight meningococcal strains which were isolated from cerebrospinal fluid or blood of patients (disease strains). Intraperitoneal (IP) iron dextran was given to some animals to enhance meningococcal virulence. After IP iron, carrier strains were still poorly invasive with rates of bacteremia ranging from 0 to 15% (mean = 3%), whereas disease-associated strains were significantly more invasive and caused bacteremia in 31–64% of animals (mean = 39%). Without iron injections, nasopharyngeal colonization rates were similar (36 versus 30%, P > 0.1) for case and carrier strains IP iron dextran significantly enhanced rates of colonization and bacteremia caused by the disease strains only. We have therefore, shown that the relative virulence of meningococcal strains for humans is maintained in this experimental model.

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Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128493 ◽

1987 ◽

Vol 45 ◽

pp. 842-843

Author(s):

V.J.A. Montpetit ◽

S. Dancea ◽

S.W. French ◽

D.F. Clapin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Paired Helical Filaments ◽

Ethanol Intoxication ◽

Drg Neurons ◽

Critical Difference ◽

Suitable Animal Model ◽

The Central Nervous System ◽

Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa155 ◽

2020 ◽

Vol 4 (11) ◽

Author(s):

Katherine M Ranard ◽

Matthew J Kuchan ◽

John W Erdman

Keyword(s):

Animal Model ◽

Vitamin E ◽

Mouse Model ◽

Wild Type ◽

Future Studies ◽

Neurological Outcomes ◽

Transfer Protein ◽

And Function ◽

The Brain ◽

Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

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Measurement of inactive renin in normal, nephrectomized, and adrenalectomized rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-205 ◽

1991 ◽

Vol 69 (9) ◽

pp. 1381-1384 ◽

Cited By ~ 4

Author(s):

Knud Poulsen ◽

Arne Høj Nielsen ◽

Arne Johannessen

Keyword(s):

Animal Model ◽

Exchange Resin ◽

Cation Exchange Resin ◽

Plasma Renin ◽

Rat Plasma ◽

Angiotensin I ◽

Renin Substrate ◽

Suitable Animal Model ◽

Inactive Renin ◽

Adrenalectomized Rats

In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues.Key words: angiotensinogen, inactive renin, renin.

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Anti-apoptotic effect of interleukin-17 in a mouse model of oxygen-induced retinopathy

Experimental Eye Research ◽

10.1016/j.exer.2019.107743 ◽

2019 ◽

Vol 187 ◽

pp. 107743 ◽

Cited By ~ 1

Author(s):

Na Li ◽

Sha Gao ◽

Jing Wang ◽

Yanji Zhu ◽

Xi Shen

Keyword(s):

Mouse Model ◽

Interleukin 17 ◽

Oxygen Induced Retinopathy ◽

Apoptotic Effect

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Aquaporin-1–Independent Microvessel Proliferation in a Neonatal Mouse Model of Oxygen-Induced Retinopathy

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.07-0537 ◽

2007 ◽

Vol 48 (10) ◽

pp. 4802 ◽

Cited By ~ 14

Author(s):

Javier Ruiz-Ederra ◽

A. S. Verkman

Keyword(s):

Mouse Model ◽

Neonatal Mouse ◽

Aquaporin 1 ◽

Oxygen Induced Retinopathy

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Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model

Journal of Virology ◽

10.1128/jvi.01383-10 ◽

2010 ◽

Vol 84 (21) ◽

pp. 11089-11100 ◽

Cited By ~ 139

Author(s):

Dennis A. Bente ◽

Judie B. Alimonti ◽

Wun-Ju Shieh ◽

Gaëlle Camus ◽

Ute Ströher ◽

...

Keyword(s):

Animal Model ◽

Mouse Model ◽

Immune Cell ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Interferon Response ◽

Laboratory Animals ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus ◽

Elevated Liver Enzymes

ABSTRACT Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation.

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Experimental model of intracranial hypertension with continuous multiparametric monitoring in swine

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130126 ◽

2013 ◽

Vol 71 (10) ◽

pp. 802-806 ◽

Cited By ~ 4

Author(s):

Almir Ferreira de Andrade ◽

Matheus Schmidt Soares ◽

Gustavo Cartaxo Patriota ◽

Alessandro Rodrigo Belon ◽

Wellingson Silva Paiva ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Animal Model ◽

Brain Injury ◽

Intracranial Pressure ◽

Intracranial Hypertension ◽

Severe Traumatic Brain Injury ◽

Transcranial Doppler ◽

Porcine Model ◽

Cerebral Oximetry ◽

Suitable Animal Model

Objective Intracranial hypertension (IH) develops in approximately 50% of all patients with severe traumatic brain injury (TBI). Therefore, it is very important to identify a suitable animal model to study and understand the pathophysiology of refractory IH to develop effective treatments. Methods We describe a new experimental porcine model designed to simulate expansive brain hematoma causing IH. Under anesthesia, IH was simulated with a balloon insufflation. The IH variables were measured with intracranial pressure (ICP) parenchymal monitoring, epidural, cerebral oximetry, and transcranial Doppler (TCD). Results None of the animals died during the experiment. The ICP epidural showed a slower rise compared with parenchymal ICP. We found a correlation between ICP and cerebral oximetry. Conclusion The model described here seems useful to understand some of the pathophysiological characteristics of acute IH.

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Mice with a humanized immune system are resilient to transplantation of human microbiota

10.1101/2021.10.06.463343 ◽

2021 ◽

Author(s):

Wei Zhou ◽

Kin-hoe Chow ◽

Rory Geyer ◽

Paola Peshkepija ◽

Elizabeth Fleming ◽

...

Keyword(s):

Animal Model ◽

Immune System ◽

Mouse Model ◽

Fecal Microbiota Transplantation ◽

Host Immune System ◽

Donor Strain ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

Human Leukocytes ◽

Human Specific

Human gut microbiota has co-evolved with human, and plays important roles in regulating the development and functioning of the host immune system. To study the human-specific microbiome-immunune interaction in an animal model is challenging as the animal model needs to capture both the human-specific immune functions and the human-specific microbiome composition. Here we combined two widely-used humanization procedures to generate a humanized mouse model (HMA-huCD34) with functional human leukocytes developed from engrafted huCD34+ cells and human fecal microbes introduced through fecal microbiota transplantation, and investigated how the two introduced human components interact. We found that the engrafted human leukocytes are resilient to the transplanted human microbes, while reciprocally the transplanted microbial community in the huCD34 mice was significantly different from mice without a humanized immune system. By tracking the colonization of human fecal Bacteroides strains in the mouse gut, we found that the composition of the strain population changes over time, the trajectory of which depends upon the type of mouse. On the other hand, different from Bacteroides, Akkermansia muciniphila exhibited consistent and rapid fixation of a single donor strain in all tested mice, suggesting strong purifying selection common to all mouse types. Our prospect study illustrated the complex interactions between the transplanted microbiome and different host factors, and suggested that the humanized mouse model may not faithfully reproduce the human-specific microbiome-immune interaction.

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Development of a Novel Human CD147 Transgenic NSG Mouse Model to test SARS-CoV-2 Infection and Immune Responses

10.21203/rs.3.rs-396257/v1 ◽

2021 ◽

Author(s):

Saiaditya Badeti ◽

Hsiang-chi Tseng ◽

Peter Romanienko ◽

Ghassan Yehia ◽

Dongfang Liu

Keyword(s):

Animal Model ◽

Mouse Model ◽

Immune Responses ◽

Viral Entry ◽

In Vivo Model ◽

High Risk Populations ◽

Functional Receptor ◽

Nsg Mouse ◽

Low Expression

Abstract An animal model that can mimic the SARS-CoV-2 infection in humans is critical to understanding the newly emerged, rapidly spreading SARS-CoV-2 and development of therapeutic strategies. Studies show that the spike (S) proteins of SARS-CoV (SARS-CoV-S-1-S) and SARS-CoV-2 (SARS-CoV-2-S) bind to human angiotensin-converting enzyme 2 (hACE2, a well-recognized, functional receptor for SARS-CoV and SARS-CoV-2) to mediate viral entry. Several hACE2 transgenic (hACE2Tg) mouse models are being widely used, which is clearly invaluable. However, the hACE2Tg mouse model cannot fully explain: 1) low expression of ACE2 observed in human lung and heart, but lung or heart failure occurs frequently in severe COVID-19 patients); 2) low expression of ACE2 on immune cells, but lymphocytopenia occurs frequently in COVID-19 patients; and 3) hACE2Tg mice do not develop strong clinical disease following SARS-CoV-2 infection in contrast to SARS-CoV-1. Moreover, one of most outstanding features of coronaviruses is the diversity of receptor usage, which includes the newly proposed human CD147 (hCD147) as a receptor for SARS-CoV-2-S. It is still debatable whether CD147 can serve as a functional receptor for SARS-CoV-2 infection or entry. Here we successfully generated a hCD147Tg mouse model in the NOD-scid IL2Rgammanull (NSG) background. In this hCD147Tg-NSG mouse model, the hCD147 genetic sequence was placed following the endogenous mouse promoter for mouse CD147 (mCD147), which creates an in vivo model that may better recapitulate physiological expression of CD147 proteins at the molecular level compared to the existing and well-studied K18-hACE2-B6 model. In addition, the hCD147Tg-NSG mouse model allows further study of SARS-CoV-2 in the immunodeficiency condition which may assist our understanding of this virus in the context of high-risk populations with immunosuppressed conditions. The hCD147Tg-NSG mouse mode can serve as an additional animal model for interrogate whether CD147 serve as an independent functional receptor or accessory receptor for SARS-CoV-2 entry and immune responses.

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