Model organism

Question 1

What are animal models? How can we use also evolutionary distant animals?

Answer 1

Animal models are used to give experimental validation to scientific hypothesis, since experiments on human are difficult do make:

• ethical concerns
• environmental and social factors
• large genome, with limited tools for genetic manipulation
• long developmental stage and lifetime with few offsprings

Question 2

Give an overview on C. elegans.

Answer 2

• Free-living non-parasitic nematode
• Body size: 1.5 mm by 80 μm
• Easy and rapid culturing, can be frozen
• 959 cells, of which 302 neuronal cells
• ~20’000 genes, 100 Mbp genome size
• Hermaphroditic (sequential)
• Essential biological functions shared with
  human: development, behaviour,
  neurobiology, aging
• Powerful genetic tools

It was used for studying the parkinson's disease:
- 302 neurons; 8 dopaminergic
- Relevant phenotypes 
(chemotaxis, loss in foraging, age
-dependent neurodegeneration)
- Transgenic tools 
- Imaging techniques

Question 3

Give an overview on D. melanogaster.

Answer 3

Very easy to culture
- Lifespan: 30-70 days, generation time: 14
days
- ~13’600 genes, 140 Mbp genome size
- Very powerful genetic tools
- Model for: development, immune response, behavior, neurobiology, evolution
- Complex organs and brain structure

It is for forward genetics: Random mutagenesis, since early 1900s
- Screen phenotypes, then identify mutation in the genome
- Chemicals, UV radiation, or transposons
- Hox genes, essential in embryonic development
- Genes involved in memory, circadian rhythm, etc.
And reverse genetics: Target-specific (transgenic) modification
- Site-directed mutagenesis
- Tissue-specific RNAi and overexpression
- Genome editing, e.g. CRISPR

Question 4

Give an overview on D. rerio.

Answer 4

• Vertebrate body plan
• Many aspects of development comparable to humans
• Short generation time, easy to culture
• ~26’206 genes, 1412 Mbp genome size
• High throughput (drug) screening
• Transparent embryos
• Not subject to regulation on animal experimentation until 5 days post fertilization

It is used for toxicology experiments and to understand the role of peroxisome proliferating-activated receptors in obese people:

• ~700 million obesity-diagnosed people (diabetes II, heart- and vascular disease, cancer)
• Hormone receptor: Peroxisome Proliferator-Activated Receptors (PPARs) regulate fat metabolism
• PPAR genetic variants are correlated with obesity prevalence

Question 5

Give an overview on M. musculus.

Answer 5

• Most commonly used animal model to study human diseases
• Evolutionary most related to humans
• Lifespan: 1.3-3 years, generation time 10 weeks
• ~24’000 genes, 2500 Mbp genome size
• Powerful tools for genetic manipulation, humanized models (PDX)
• Due to placentation the study of mammalian embryology is difficult

Question 6

How can we chose an animal model?

Answer 6

• Biological suitability
• Genetic information
• Research practicality: genome size, biological complexity, life history, robustness, diet, amenability, ease of rearing, etc
• Existing laboratory procedures & experimental techniques

Question 7

Why results from model organisms need to be interpreted with caution?

Answer 7

Evolutionary conserved does not mean “identical”:

• Even “basic” metabolic pathways can vary due to species-specific evolutionary adaptation
• Significant differences in immune systems between mice and humans:
• Distribution of tumors differs between mice and humans
• Mice often respond markedly different to experimental (drug) interventions than humans