Lecture 18 - Using animal models to investigate genetic effects on behaviour

Question 1

What is an animal model?

Answer 1

A living, non-human organism used to study the biological basis of human traits and disorders, aiming to understand and alleviate pathological conditions without risking human harm

Question 2

What are the criteria for a good animal model?

Answer 2

• Face validity: The model resembles the human phenotype
• Construct validity: The model and human condition share underlying biological mechanisms
• Predictive validity: Therapeutic interventions have similar effects in both the model and humans, allowing for effective treatment screening

Question 3

What are the main types of animal models?

Answer 3

Surgical: Procedures like middle cerebral artery occlusion (stroke), brain lesions, and gonadectomy
- Chemical/ Biological/ Radiation: Use of agents like Metrazol for epilepsy, immunisation with autoimmune disorders, administration of pathogens to study infectious diseases, and neurotransmitter modulators
- Genetic: Manipulation of genomic DNA or administration of genetic material to affect gene expression

Question 4

What are the advantages of using animal models to understand gene function and dysfunction?

Answer 4

• Ability to examine in vivo effects of brain function and behaviour
• Ethical feasibility of procedures not possible in humans
• Maintenance of large colonies and controlled genetic backgrounds
• Short generation times and good breeding capabilities
• Genetic similarity to humans and amenability to genetic manipulation
• A wide range of sophisticated behaviours for study

Question 5

What are the disadvantages of using genetic animal models?

Answer 5

• Genetic and physiological differences from humans
• Different evolutionary histories affecting sensory modalities and social behaviours
• Limited range of genetic modifications possible
• Challenges in modelling complex human behaviours influenced by multiple genes (endophenotypes)
• Ethical concerns regarding adverse effects and ionability to model human-specific traits like language

Question 6

Which species are commonly used as genetic animal models?

Answer 6

• Caenorhabditis elegans (nematode worm): Transparent body, defined cell lineage, simple nervous system
• Drosophila melanogaster (fruit fly): Simple genome, used for studying neurodegenerative disorders and behaviours
• Danio rerio (zebrafish): Transparent embryos, rapid development, used for developmental and behavioural studies
• Mus musculus (mouse) and Rattus norvegicus (rat): Mammalian models iwth high genetic similarity to humans, used for a wide range of behavioural studies
• Prairie and meadow voles: Studied for social bonding behaviours
• Genetically modified non-human primates: Rare but used for specific studies

Question 7

What are the genetic manipulation techniques used in rodents?

Answer 7

Selective Breeding: Inbreeding for genetic homogeneity; outbreeding for genetic diversity
- Gene knockout: Removal of specific genes to study their function; can be conditional
- Transgenesis: Insertion of exogenous genes to study overexpression effects
- Knock-in: Replacement of a gene with a mutated version to study specific mutations
- Mutagensis: Use of chemicals or radiation to induce random mutations, followed by selective breeding
-Chromosomal mutations: Study of spontaneous or induced chromosonal changes, such as in Down syndrome models

Question 8

How can gene/protein expression be transiently altered in animal models?

Answer 8

• Introduction of molecules like antisense oligonucleotides, siRNAs, or morphosinos to inhibit transcription/translation
• Use of drugs that alter the epigenome, such as sodium butyrate

Question 9

What are some new genetic technologies used in animal models?

Answer 9

• CRISPR/Cas9: RNA-guided genome-editing tool for precise genetic modifications
• Optogenetics: Use of light-sensitive proteins to cotnrol neuronal activity with light
• DREADDs: Designer receptors activated by designer drugs to modulate specific neural circuits

Question 10

Summary: Why are animal models valuable for studying genetic effects on behaviour?

Answer 10

They offer controlled environments for genetic manipulation, allowing researchers to study the in vivo effects on brain function and behaviour, which is often not feasible in human studies due to ethical constraints