Animal models Flashcards
What types of animals are covered under EU Directive 2010/63 for animal experiments?
Live vertebrate animals, including independently feeding larvae and fetal forms in the last third of gestation.
When is an experiment considered an “Animal Experiment” under EU Directive 2010/63? (3)
When it involves any invasive or non-invasive use of a live vertebrate animal for scientific or educational purposes, causing pain, discomfort, or distress.
What are some examples of animal experiments under EU Directive 2010/63? (4)
Drug administration, surgical procedures, disease induction, and behavioral studies causing discomfort.
What key information about objectives should be provided to the Ethical Committee (DEC) for an animal experiment? (3)
A clear primary objective, including long-term goals and specific research questions for the next five years.
What must be included in the description of procedures for an ethical review? (6)
Type of procedure
Frequency and duration
Recovery and aftercare
Impact severity classification
Control groups and experimental design
How should the use of animals be justified for an ethical review?
By explaining why non-animal alternatives cannot be used and why animal models are necessary.
What is the role of the Three R’s in an ethical review?
Replacement: Why non-animal methods can’t be used.
Reduction: How animal numbers will be minimized.
Refinement: How animal suffering will be reduced.
What outcome parameters should be included for the Ethical Committee? (5)
Primary outcome: The main result or effect that the experiment aims to measure, such as tumor size, behavioral changes, or survival rate.
Secondary outcomes: Additional effects that will be measured, like biochemical markers, side effects, or histological analysis.
Causal link: Demonstration of a cause-effect relationship between the intervention (e.g., drug administration, surgery) and the observed outcomes.
Correlation with human relevance: Explanation of how the outcomes observed in the animal model relate to the expected outcomes in humans (if applicable).
Time frame for outcomes: When and how often measurements will be taken to observe the effects, ensuring that outcomes are measurable and timed appropriately for valid data.een variables.
What are some pros of using experimental animals in research? (4)
Controlled variables - genetics, environment, previous exposure. Allows for precise manipulation of variables
Animal models: modification of animals to mimic human disease
Invasive studies or long-term studies - ie. surgeries or drug testing, not as easy in humans
Ethical feasibility - some experiments may not be ethical to perform on humans (i.e. toxicity or severe disease models)
What are some cons of using experimental animals in research? (4)
Species differences - can limit relevance to humans
Ethical concerns - Cannot consent, may suffer pain and discomfort
High costs and time consumption - require specialized facilities, care, regulatory compliance
Publication bias - negative results are often unreported, leading to repeats and unnecessary use of animals
What are pros of using human beings in research? (4)
-Direct relevance to human physiology and health
-Informed consent - voluntary participation and ethical transparency
-No species differences
-Diverse data including genetic, environmental and lifestyle background (may be relevant to human disease)
What are cons of using human beings in experiments? (4)
Ethical limitations: limitations in types of invasive or harmful procedures, restricts research scope
High variability: due to genetic, environmental and lifestyle variability - harder to control for confounding factors
Limited long-term of invasive studies
Higher risks that are hard to manage due to requirement of strict oversight
Why are human studies often more variable than animal studies?
Humans have high genetic and environmental variability, making it harder to control for confounding factors.
What is the definition of an animal model in research?
A living organism used to induce a pathological process for the purpose of investigating human biology and diseases, often mimicking human responses for research.
What are some of the main uses of animal models in research? (4)
- Characterizing pathogens
- Studying mechanisms of diseases
- Testing intervention strategies
- Understanding biological processes
What makes animal models controversial yet valuable?
Animal models are controversial due to ethical concerns about animal use in research, but they remain highly valuable if experiments are conducted with precision, following ethical guidelines and regulations.
What are the three (3) key responsibilities a researcher must have when conducting animal experiments?
- Knowledge of regulations
- Practical skills to conduct experiments
- Awareness of animal welfare and ethical considerations
What is the process of applying for permission to conduct animal experiments? (4)
- Writing a detailed proposal for a Central Commission for Animal Experiments (CCD) license.
- Receiving feedback from the Animal Welfare Body (ABB).
- Submitting the proposal to a national project evaluation body (DEC).
- Revising and resubmitting until the experiment is approved.
What are the 3 R’s that researchers should consider when designing an animal experiment?
Replacement: Can the experiment be conducted without using animals?
Reduction: Can fewer animals be used while still obtaining valid results?
Refinement: Can procedures be refined to minimize discomfort and enhance animal welfare?
What are the ARRIVE guidelines?
A set of standards that detail how animal experiments should be designed and reported to ensure that they can be reproduced and validated by other researchers.
What are some factors to consider when choosing an animal model?
- Species: Which species is most appropriate for the research question?
- Age, Sex, and Genetics: Does the age, sex, or genetic background affect the results?
- Microbiological Status: Are the animals pathogen-free, or do they have relevant infections/co-morbidities?
- Behavior: How does the behavior of the species affect the outcome?
What are some commonly used animal models for studying human coronaviruses? (4)
Non-human primates: Used for their similarity to humans, though expensive and ethically sensitive.
Ferrets: Often used for respiratory viruses like influenza and SARS-CoV.
Hamsters: Commonly used for SARS-CoV-2 studies due to their ability to mimic human respiratory symptoms.
Transgenic mice: Genetically modified to express human receptors like ACE2 to study SARS-CoV and SARS-CoV-2.
What factors influence the outcome of animal experiments studying coronaviruses? (4)
Age: Older animals may show more severe symptoms.
Sex: Male animals often exhibit more severe outcomes than females.
Comorbidities: Conditions like obesity, diabetes, and immune deficiencies influence disease severity.
Species: The choice of species affects how closely the model mimics human responses.
What are the complexities of designing an animal experiment for zoonotic coronaviruses? (4)
- Host-virus interactions: The receptor diversity between species can impact susceptibility.
- Viral strain: Different strains of a virus can have different levels of infectivity and pathogenicity.
- Immune response: Host immune responses vary across species and can affect the disease outcome.
- Transmission pathways: Designing models that accurately replicate natural transmission is challenging.
What components make up an animal model to study a disease? (4)
An animal model includes not only the (1) animal species but also (2) the specific aspect of the disease being studied, (3) the pathogen, and the (4) methodology (e.g., dose and inoculation route).
Why are ferrets the animal species of choice to study the pathogenesis of influenza viruses? (4)
Ferrets are (1) highly susceptible to both human and zoonotic influenza viruses, (2) show similar disease progression and symptoms to humans, and (3) have similar lung anatomy and virus-associated pathological changes. (4) They also have comparable receptor distribution for flu virus attachment.
What are important criteria to consider when selecting the components of an animal model?
Key criteria include (1) the susceptibility of the species to the pathogen, (2) anatomical and histological similarities, (3) immune response, (4) the aspect of the disease being studied, (5) pathogen characteristics (e.g., wild-type vs. recombinant), and (6) methodological considerations like dose and time points.
How does the methodology impact the design of an animal model?
Methodology, such as the inoculation dose and route, affects where the infection occurs (e.g., upper vs. lower respiratory tract), the severity of the disease, and the reproducibility of results. Adjustments are made to ensure consistent infection and to match the study’s research goals.
What is a common methodological adjustment made when designing animal models for respiratory infections?
In respiratory infection models, researchers often choose intratracheal inoculation to ensure the virus reaches the lower respiratory tract, especially when studying pneumonia. Intranasal inoculation may be used for studies focused on upper respiratory tract infections or transmission studies.
Why is it important to adjust the dose of the pathogen in animal experiments?
A higher dose is often used in animal studies to ensure all subjects are infected, which is crucial for statistical significance, especially when studying vaccine protection or other interventions.
What factors influence the selection of time points for sample collection in animal experiments?
Time points are selected based on the progression of the disease in both humans and animals. Acute diseases like flu may require earlier time points, while slower-progressing diseases may need later points to capture key stages of pathology and immune response.
What factors influence the selection of time points for sample collection in animal experiments?
Time points are selected based on the progression of the disease in both humans and animals. Acute diseases like flu may require earlier time points, while slower-progressing diseases may need later points to capture key stages of pathology and immune response.
What makes ferrets a reliable model for both human and zoonotic influenza viruses? (3)
Ferrets share similar (1) virus attachment patterns, (2) receptor distribution, and (3) lung pathology with humans, making them reliable for studying natural infections without the need for viral adaptation, which is often required in other species like mice.
Why is it important to align an animal model, like the ferret model, to a specific research question in disease studies?
An animal model must be aligned to the research question to effectively mimic the aspect of the disease being studied, such as airborne transmission between humans, ensuring the model provides relevant and accurate insights.
What are the three key principles of the 3R approach in animal experiments?
Refinement: Improving the methods to reduce suffering and improve data quality.
Reduction: Using fewer animals while obtaining quality data.
Replacement: Using alternatives to animal testing where possible.
What are some positive aspects of the ferret model for studying influenza transmission?
The ferret model is useful because ferrets are susceptible to natural infections, have similar airway anatomy and pathology to humans, and exhibit virus attachment patterns akin to humans, making it a reliable model for airborne transmission studies.
What is a potential limitation of using ferrets for studying contact transmission of diseases?
Ferrets are very social animals and in experiments tend to stay close together, which may not accurately reflect human behavior during contact transmission, leading to less realistic outcomes for human disease modeling.
How does humidity affect virus transmission in the guinea pig model?
Transmission efficiency of influenza viruses in guinea pigs varies with humidity. It is more efficient at low humidity, decreases at around 50%, and increases again at very high humidity, illustrating how environmental factors influence transmission.
What did air sampling studies in ferrets reveal about the infectious period for influenza?
Air sampling studies showed that peak airborne virus shedding occurs around day two after infection and drops quickly, suggesting that even though a ferret may still be PCR positive, it may not remain contagious throughout the entire sickness period.
How do small and large aerosol particles differ in their role in virus transmission?
Small aerosols can remain airborne for longer periods, allowing them to travel further distances, while large droplets tend to fall to the ground more quickly due to gravity, limiting their role in distant airborne transmission.
How was the concept of virus transmission by fur tested in ferrets?
Researchers vaccinated ferrets to prevent nasal infection, applied a virus to their fur, and found that transmission still occurred, suggesting that fur contamination could contribute to virus spread even without respiratory infection.
What are the advantages and challenges of using guinea pigs as models for influenza transmission studies?
Guinea pigs are easier to handle, less likely to bite, and require smaller spaces, but they are less experienced as models, and their pathogenesis differs from that of ferrets, presenting a challenge for studying transmission dynamics.
What did experiments testing SARS-CoV-2 transmission in ferrets reveal about airborne transmission?
Experiments showed that SARS-CoV-2 could be transmitted via the air in ferrets, similar to H1N1 influenza, suggesting that the virus can remain infectious while airborne over a distance greater than one meter.
