Animal model
INTRODUCTION
- Animal – Latin- soul/spirit
- Model – object of imitation- something that accurately resembles something else
- Animal model – animated object of imitation – investigate a physiological or pathological circumstance
ANIMAL MODEL
- Living organism – animal
- Normative biology / behaviour can be studied,
- Spontaneous / induced pathological process can be investigated,
- Phenomenon resembles humans or other species of animal
USE OF ANIMAL MODEL
- Assessment of pathogenic mechanisms
- Diagnostic and therapeutic procedures
- Nutrition and metabolic diseases
- Efficacy of novel drug development
TYPES OF ANIMAL MODELS
- Exploratory – understanding of normal / abnormal fundamental biological mechanisms.
- Explanatory – understanding of complex biological problems.
- Predictive – Discover and quantify the impact of investigative treatments whether for diseases or chemical toxicities
DISEASE RELATED ANIMAL MODEL
- Induced (experimental) – experimentally created either through surgical modifications, genetic modifications, or chemical injections.
- Spontaneous – genetic variants, which mimic the human condition. Variance occurs naturally through mutation and not by experimental induction.
- Transgenic – induced models in which DNA is inserted into or deleted (knockout) from the genome of the animal.
- Negative – negative models fail to react to a disease or chemical stimulus. Studies on the mechanism of disease resistance.
- Orphan – opposite of negative models – disease occurs but there is absence of corresponding disease in humans.
- Orphan models – become induced models when a similar disease is recognized in humans.
SUBCATEGORY
- Fidelity – the extent a biological structure in an animal resembles that of a human.
- Homologous – symptoms shown in the animal are identical to those shown in the human.
- Isomorphic – animal’s symptoms or anatomy are similar to those in the human but the etiology or genetic character is different.
SUBCATEGORY
- Partial – these models do not mimic the entire human disease but enough similarities exist to allow their use in studying aspects of the disease or treatments.
- Face validity – the degree to which there is a similar phenotypic display between the disease in the animal and the corresponding disease in the human.
- Construct validity – the degree to which there is a similar genetic display between the disease in the animal and the corresponding disease in the human.
CHOOSING THE RIGHT MODEL
- Research factors
- Animal care factors
- Physical and environmental factors
- Animal-related factors
- RESEARCH FACTORS
- Appropriateness as an analogue – the part or organ being studied has function similar to target species.
- Transferability of information – define a process in a system with the hope of transferring the data gained to a more complex system.
- Generalizability of the results – the ability to generalize results to the target species.
- Ethical implications – certainly research must start with justification for using an animal.
- Numbers needed – numbers needed to provide scientific validity.
- Customary practice within a particular discipline.
- Existing body of knowledge of the problem – thorough literature search before forming basis for the research project.
- Natural versus experimentally produced models -unavailability of natural models will require the use of experimentally produced models.
- ANIMAL CARE FACTORS
- Cost and availability
- Housing availability
- Husbandry expertise
- Stress factors – transportation, handling and manipulations, overcrowding, lack of environmental enrichment, and the research project itself.
- PHYSICAL / ENVIRONMENTAL FACTORS
- Ecological consequences – ecological consequences must be considered in its removal.
- Hazardous components – use of chemicals, infectious agents, and radioisotopes.
- Environmental influences – environmental factors -physical, chemical, biological, and social may impact the physiological and behavioural. Humidity, ventilation, light cycle and quality, noise, cage size and bedding materials, diet and water, and room temperature.
- ANIMAL-RELATED FACTORS
- Genetic aspects – uniformity of organisms may be necessary where applicable
- Background knowledge of biological properties – knowledge of biological properties – generalized and specialized function of body components is needed.
- Ease of and adaptability to experimental manipulation.
- Size of the animal – size of the animal impacts housing and husbandry availability.
- Life span and age.
- Progeny in a single birth.
- Diseases or conditions that might complicate results.
- Special features of the animal such as unique responses or micro flora. It is important to be familiar with unique anatomical or physiological features of the species.
EXTRAPOLATION TO HUMANS
- Key factor -animals in research -extrapolation of results to humans.
- Plurispecies approach – two species in toxicology screening, one of which has to be non rodent.
- Metabolic patterns and speed and body size must match between species.
- Experimental design and the life situation of the target species must correspond.
DESCRIPTION OF ANIMAL MODEL
- Genetic strain and sub strain using correct international nomenclature
- Special genetic features
- Microbial status of the animal
- Age
- Housing standards
- Maintenance procedures
- Diet