0. Model selection

• What model system is used? Why is this system appropriate for the study’s goals (e.g., relevance to human biology, ease of manipulation)? • What are alternative model systems? Compare their pros/cons (cost, ethical concerns, translatability). • Are there ethical considerations in using this system? Models: - In silico model - Cell line model - Mouse model(animal model) - Human model

3R for animal model

And the choice should follow the 3Rs principle: Replacement, Reduction, and Refinement - Replacement: we should use alternatives to replace live animals when possible, like cell cultures, computer models - Reduction: we should minimizing the number of animals used while maintaining scientific validity - Refinement: we should optimize procedures to minimize pain and distress, improving animal welfare through better housing, enrichment, and less invasive techniques

In silico models

• Advantage:
  • useful for predicting gene functions, drug interaction, pathway by calculation
  • cost-effective
  • rapid for initial screening
• Disadvantages
  • Limited by accuracy of algorithms, and limited by existing knowledge and datasets
  • Can only be used to raise up hypotheses or identify wet lab results

Cell line model

• Cell line models use cultured cells (often immortalised) to study biological processes in controlled environments
• Advantages:
  • More biologically relevant than computational models
  • Controlled experimental environment
  • Relatively inexpensive compared to animal/human studies
  • Amenable to high-throughput screening
  • Allows for genetic manipulation and specific pathway analysis
  • Reproducible results from homogeneous populations
  • Can be used in pilot experiment to decide which method or does of drug could be the best.
• Disadvantages:
  • Lack complex tissue interactions and physiological context
  • May not represent in vivo behavior accurately
  • Cell lines can drift genetically over passages
  • Limited to cellular responses rather than organism-level effects
  • May not reflect normal cell behavior (especially cancer cell lines)
  • Cannot study systemic responses or organ interactions

Mouse model

• 8 weeks -- young and adult mouse
• Advantages:
  • Whole organism with intact physiological systems
  • Significant genetic similarity to humans (~85%)
  • Well-characterized biology and available genetic tools
  • Allows study of complex disease processes and treatments
  • Enables tissue interactions and systemic responses
  • Established protocols and research precedents
• Disadvantages:
  • Expensive to maintain and require specialized facilities
  • Significant ==ethical== considerations and regulatory requirements
  • Physiological differences from humans affect translatability
  • Longer experimental timelines than in vitro studies
  • Genetic homogeneity in lab strains may not reflect human diversity
  • Limited sample sizes due to cost and ethical considerations

Human Models

• Advantages
  • Directly relevant to human health and disease
  • No species translation concerns
  • Captures human-specific biological responses
  • Most valuable for clinical applications
  • Reflects human genetic and physiological diversity
• Disadvantages:
  • Highest ethical scrutiny and regulatory requirements
  • Most expensive and logistically complex
  • Limited experimental manipulation possibilities
  • Significant variability between individuals
  • Longer timelines for study completion
  • Recruitment and retention challenges
  • Limited ability to control for confounding variables

Zebrafish Model

• Advantages:
• Transparent embryos allow real-time visualization of development
• Rapid development and short generation time
• High fecundity (hundreds of embryos per mating)
• External fertilization and development
• ~70% genetic similarity to humans
• Amenable to genetic manipulation (CRISPR, transgenesis)
• Relatively low cost compared to mammalian models
• Less stringent ethical regulations than mammalian models
• Disadvantages:
• Evolutionary distance from humans limits some applications
• Physiological differences in some organ systems
• Limited behavioral complexity compared to mammals
• Some human disease mechanisms not conserved
• Regenerative abilities not shared with humans

Rat Model

• Advantages:
• Larger size than mice allows for more complex surgical procedures
• Better for behavioral and cognitive studies than mice
• More similar to humans in some physiological and metabolic aspects
• Superior model for certain disease areas (cardiovascular, neurological)
• Well-established in toxicology and drug development
• More sophisticated social behaviors than mice
• Disadvantages:
• More expensive than mice
• Fewer genetic tools available compared to mice
• Require more space and resources
• Similar ethical considerations as mice
• Still significant translational gaps to humans

Non-Human Primate Models

• Advantages:
• Closest evolutionary relationship to humans
• Similar brain structure and cognitive abilities
• Comparable immune system and disease susceptibility
• Most predictive for human drug responses and safety
• Critical for specific research areas (neuroscience, infectious disease)
• Similar reproductive physiology
• Disadvantages:
• Highest ethical concerns among animal models
• Extremely costly to maintain
• Stringent regulatory requirements
• Long lifespan complicates longitudinal studies
• Limited availability and specialized facility requirements
• Public controversy surrounding their use

Drosophila (Fruit Fly) Model

• Advantages:
• Rapid generation time (10-12 days)
• Extensive genetic tools available
• Low cost and easy maintenance
• ~60% of human disease genes have fly counterparts
• Minimal ethical concerns
• High-throughput screening capability
• Well-characterized developmental biology
• Disadvantages:
• Significant evolutionary distance from humans
• Simplified organ systems
• Invertebrate physiology differs substantially from mammals
• Limited behavioural complexity
• Restricted ability to model complex human diseases