Exam 1 - Animal Models

Question 1

What are the benefits of using animals in research and how is animal research regulated?

Answer 1

• treatments for major diseases
• mutually beneficial for humans and animals due to new discoveries in animals too
• reduce disease symptoms and impact of nutrition on biomarkers related to disease
• control variables – genetics, and environment
• mechanism of action - cause & effect
• opportunity to test an intervention that can cause illness pain or even death (must be justified)

Question 2

What is IACUC and its purpose?

Answer 2

o IACUC committees approve animal protocol to minimize any suffering the animal would experience
o Inspect all animal facilities
o Ensure faculty, students, staff are trained on techniques
o Report misuse/non-compliance to OLAW

Question 3

What factors can be manipulated when using mice for research?

Answer 3

• Genotype – gene knockout, transgenic mice, selective breeding
• Phenotype
• Environment
• Diet: disease development and progression

Question 4

How can gene function be manipulated in transgenic mice?

Answer 4

• Mutant gene – change in DNA sequence
• Knock out (-/-) – not expressed
• Overexpression – excessively high amounts of the gene are being expressed

Question 5

Briefly, describe the cre-lox system for transgenic mice and the advantages of using the cre-lox system.

Answer 5

• One parent has the LoxP site, inserted using homologous recombination
• One parent has the cre-recombinase (Cre)
• Cre cuts the LoxP
• When these mice breed it forms a knockout mouse in the offspring
• **Advantages: The promotor turning on Cre expression is often tissue specific - can look at the role of genes in specific cells **

Question 6

Two examples of the cre-lox system were explained (prostate cancer and osteoclasts). Select one of the examples and explain how the cre-lox system was used.

Answer 6

• P10 model of prostate cancer
• Creating a mouse that has cre-p10 and recognizes LoxP
  o Tamoxifen inducible – meaning the process can be controlled through this injection to start the process of gradual reduction of p10 in mice
  1. 3 weeks - 7 on low fat diet, 9 on high fat diet
  2. 6 weeks – tamoxifen injection performed
  3. 14 weeks later – looked at outcomes including:
  a. pathology – tissues analyzed to look for PIN development
  b. Interleucan 6