Lecture 19 - Using animal models to investigate genetic effects on behaviour

Question 1

(lecture):

What is an animal model?

What are the 3 criteria for a good animal model?

Answer 1

(lecture):

‘A living, non-human being used to understand the biological basis of healthy and pathological human phenotypes, and how to alleviate the latter, without the risk of harming an actual human being during the process’

See slide 2

Question 2

(lecture):

What are the different types of animal models?

Answer 2

(lecture):

See slide 3

Question 3

(lecture):

What are some advantages of using animal models to understand gene (dys)function?

Answer 3

(lecture):

See slide 4

Question 4

(lecture):

What are some disadvantages of using animal models to understand gene (dys)function?

Answer 4

(lecture):

See slide 5

Question 5

(lecture):

List some commonly used genetic animals models.

Answer 5

(lecture):

See slide 6

Question 6

(lecture):

Describe C. elegans in regards to why we use them as animal models.

Answer 6

(lecture):

See slide 7

Question 7

(lecture):

Describe D. melanogaster in regards to why we use them as animal models.

Answer 7

(lecture):

See slide 8

Question 8

(lecture):

Describe Zebrafish in regards to why we use them as animal models.

Answer 8

(lecture):

See slide 9-10

Question 9

(lecture):

Describe Rodents (mice and rats) in regards to why we use them as animal models.

Answer 9

(lecture):

See slide 11

Question 10

(lecture):

List a few ways that we can modify the rodent genome to assess effects on brain and behaviour.

Answer 10

(lecture):

See slide 12

Question 11

(lecture):

Describe selective breeding in rodents used to modify the genome to assess effects on brain behaviour.

Answer 11

(lecture):

See slide 13-14

Question 12

(lecture):

Describe gene knockout in rodents used to modify the genome to assess effects on brain behaviour.

Answer 12

(lecture):

See slide 15

Question 13

(lecture):

Describe transgenesis in rodents used to modify the genome to assess effects on brain behaviour.

Answer 13

(lecture):

See slide 16

Question 14

(lecture):

Describe Mutagenesis using chemicals (‘phenotype-driven approach’) in rodents used to modify the genome to assess effects on brain behaviour.

Answer 14

(lecture):

See slide 17

Question 15

(lecture):

Describe Chromosomal mutations in rodents used to modify the genome to assess effects on brain behaviour.

Answer 15

(lecture):

See slide 20-21

Question 16

(lecture):

Read slide 18-19

Answer 16

(lecture):

Question 17

(lecture):

Describe mouse model for down syndrome in rodents used to modify the genome to assess effects on brain behaviour.

Answer 17

(lecture):

See slide 22

Question 18

(lecture):

Describe Administration of molecules affecting gene/protein expression in rodents used to modify the genome to assess effects on brain behaviour.

Answer 18

(lecture):

See slide 23

Question 19

(lecture):

Read slide 24 onwards

Answer 19

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Question 20

(lecture):

Summary

Animal models offer greater experimental control and amenability than human studies for examining genetic effects on behaviour

There are a number of commonly used genetic animal models, each with its own set of advantages and disadvantages

Alterations to the genomic DNA sequence can lead to absence of gene expression (‘knockout’), altered gene function (‘knockin’) or increased gene expression (‘transgenesis’); these changes can be made to occur at selected timepoints/in selected tissues (‘conditional’ approaches)

Brain gene expression can also be altered in a specific manner by introducing small genetic sequences that impair transcription and/or translation

New genetic techniques (e.g. CRISPR, optogenetics and DREADDs) are revolutionising our knowledge about the genetic substrates and neural circuitry underlying particular behaviours

Answer 20

(lecture):

Question 21

(reading):

Yizhar (2012) Optogenetic insights into social behaviour function Biol Psychiatry 71(12):1075-80

Walters et al. (2016) Advanced in vivo use of CRISPR/Cas9 and antisense DNA inhibition for gene manipulation in the brain Front Genet 6:362

Answer 21

(Reading):