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NUTR 606 Research Methods > Animal Models > Flashcards

Animal Models Flashcards

(41 cards)

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1
Q

What are the uses of animals in scientific research?

A
  • fundamental research
  • medial or clinical studies
  • development of products or devices
  • regulatory testing
  • educational purposes
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2
Q

What are some considerations regarding animal research?

A
  • some research with animals is conducted specifically for the purpose of improving animal health
  • most animal research is conducted primarily for the benefit of humans, not animals
  • animals cannot consent to participate in experiments or comment on their treatment (unlike humans)
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3
Q

How does the scientific community see animal research?

A
  • recognize limitations of animal models

- point to their valuable contribution to knowledge and human health.

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4
Q

What does the CCAC stand for?

A

Canadian Council on Animal Care

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5
Q

What is the function of CCAC?

A
  • setting an maintaining standards for the care and use of animals in science
  • autonomous and independent body
  • guidline documents and policy statements
  • accountable to general public
  • responsible to disseminate information
  • compiles statistics on animal use
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6
Q

What are the categories of invasiveness?

A

Categories of invasiveness are based on a precautionary approach and protocols are assigned a category according to the potential level of pain and distress that the animals might experience

A. involve tissue, tissue culture, eggs, invertebrates, protozoa…

B. little or no discomfort or stress
C. minor stress or pain of short duration
D. moderate to severe distress or discomfort
E. severe pain near, at, or above the pain tolerance threshold of unanesthesized conscious animals

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7
Q

What is the 3R principle?

A

Replacement - use of non-animal models such as microorganisms or cell culture techniques, computer simulations, or species on the phylogenic scale

Reduction - use methods aimed at reducing the numbers of animals such as minimization of variability, appropriate selection of animal model, minimization of animal loss, and careful experimental design

Refinement - eliminate or reduce unnecessary pain and distress

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8
Q

Describe the 3 groups of the animal welfare

A
  1. basic health and functioning
  2. affective states of animals (enjoy their lives)
  3. ability to perform important types of natural behavior
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9
Q

What are the 5 freedoms?

A
  • hunger and thirst
  • discomfort
  • pain, injury, and disease
  • express normal behavior
  • fear and distress
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10
Q

What is distress, discomfort, and pain?

A

distress:
state associated with invasive procedures conducted on an animal, or with restrictive or other conditions which significantly compromise the welfare of an animal

discomfort:
mild form of distress

pain:
unpleasant sensory and emotional experience associated with actual or potential damage

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11
Q

What are the advantages of using rats?

A
  • cheap to buy
  • cheap to house
  • omnivorous
  • compliant to changes in diet
  • availability of specific, well-defined genetic strains
  • well defined nutritional requirements
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12
Q

What are the disadvantages of using rats?

A
  • short life-span
  • not susceptible to some chronic diseases associated with human aging
  • differences in the GI system (no gallbladder, well-developed cecum)
  • differences in metabolism (higher lipogenesis in adipose and liver, higher hepatic cholesterol synthesis, lower plasma cholesterol)
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13
Q

What are the advantages and disadvantages of using mouse in research?

A

same as rats

advantages:
- cheap to buy
- cheap to house
- omnivorous
- compliant to changes in diet
- availability of specific, well-defined genetic strains
- well defined nutritional requirements

disadvantages:

  • short life-span
  • not susceptible to some chronic diseases associated with human aging
  • differences in the GI system (no gallbladder, well-developed cecum)
  • differences in metabolism (higher lipogenesis in adipose and liver, higher hepatic cholesterol synthesis, lower plasma cholesterol)
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14
Q

What are some other advantages of using mouse in research other than the ones from rats?

A
  • many strains with different phenotypes and disease susceptibility (interaction between genotypical, phenotypical, and environmental influences on disease progression
  • genetic manipulation: knock-out or overexpress genes
    (- effects of specific genes on susceptibility to disease
  • relationship between genetic and environmental influences
  • polygenic nature of many chronic diseases)
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15
Q

What are some other animals that can be used in research and for what purposes?

A

rabbits, guinea pigs, hamsters

  • exhibit some phenotypes relevant to human biochemistry/physiology
  • not widely used

farm animals
- to improve efficiency of human food production

pigs

  • omnivorous, longer lifespan
  • many similarities to humans
  • expensive
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16
Q

Animal models of chronic diseases

A

CVD
Obesity
Diabetes
Cancer

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17
Q

Explain CVD studies on animals

Study These Flashcards
A
  • multifactorial disease
  • animal models exist, none-mimics the entire disease progression
  • humans: develop over decades
  • animals: can only study over a few months
18
Q

CVD “Normal” animal models

Study These Flashcards
A

Mostly HDL: mouse, rat

Mostly LDL: guinea pig

19
Q

Which animals are closer to humans in terms of CVD?

Study These Flashcards
A

hamster, rabbit

20
Q

Which animals are the closest to humans in terms of CVD?

Study These Flashcards
A

pig and chimps

21
Q

How to induce atherosclerosis in animals?

Study These Flashcards
A

They will not develop it on their own unless they are fed with high saturated fat or trans fat diet

22
Q

What happens to rabbits when we induce CVD through diet?

Study These Flashcards
A
  • Develop hypercholesterolemia and atherosclerotic lesions

- hyperlipidemia different from humans

23
Q

What happens to rats when we induce CVD through diet?

Study These Flashcards
A

they are pretty resistant

24
Q

What happens to mouse when we induce CVD through diet?

Study These Flashcards
A

depends on the strain:

  • lesions develop in different areas than humans
  • small coronary arteries
  • different strains –> can identify candidate genes involved in atherosclerosis
25
What happens to hamster when we induce CVD through diet?
◦Human-like VLDL with only Apo B100 ◦Rats & mice: Apo B48 and 100 ◦Used to show that dietary FA regulate LDL uptake after interaction with LDL receptors in liver ◦SFA & transFA --> decreased expression of LDL receptors--> increased LDL
26
What are the pros and cons of Apo E-/- mouse?
Pros: ◦ Impaired clearance of VLDL & VLDL remnant particles ◦ Spontaneously develop lesions Cons: ◦ Other functions of ApoE: macrophage fct, immune fct, adipose tissue ◦Limited use in nutrition research
27
What are the pros of Apo E*3 leiden mouse?
- Diet-induced atherosclerosis | - Other ApoE functions unaffected
28
What are the pros and cons of LDLr-/- mouse?
Pros - Model of familial hypercholesterolemia - Absence or reduced LDL receptors --> decreased clearance of LDL - Develop atherosclerosis when given high chol/high fat diet Cons: - No LDL receptor, but dietary FAs regulate the expression of this receptor!
29
Explain obesity
Excessive accumulation of adipose tissue - Energy consumption > energy expenditure - Associated with insulin resistance - Hypertriglyceridemia, low HDL, high BP, high FBG =metabolic syndrome - Associated with increased risk of diabetes and CVD
30
Animal models: diet-induced obesity
* Most species: inherent mechanisms to reduce food intake in response to high energy density * Response to high-fat feeding is poorly regulated - Lead to increase in energy consumption - Increased palatability of food = E.g.“Cafeteria diet"
31
ob/ob mouse
- Single base pair deletion in leptin gene - Uncontrolled food intake - Obesity, insulin resistance, eventually diabetes
32
db/db mouse
- Mutation in leptin receptor | - Obesity at 1 month, hyperglycemia at 2 months
33
Zucker Fatty Rat (ZFR)
- Mutation in leptin receptor - Uncontrolled food intake, obesity, insulin resistance - Substrain: Zucker diabetic fatty (ZDF) rat develops diabetes
34
Agouti lethal yellow mouse
◦Mutations in agouti gene ◦Agouti protein competes with alpha-melanocyte-stimulating protein, an anorexigenic factor ◦Obesity occurs in adult life ◦HTN
35
New Zealand obese mouse
- Increased food intake, obesity at 2 months - Males develop type 2 diabetes - Reduced activity leves
36
Strains susceptible to DIO, insulin resistance and atherosclerosis
◦ E.g. ob/ob or db/db mice with LDLr-/-mice | ◦ E.g. JCR:LA cp rat –metabolic syndrome, arterial lesions
37
How to induce cancer in animals for studies?
◦ Chemically induced ◦ DMBA:1,2-dimethylbenz(a)anthracene --> breast ◦ DMH:1,2-dimethylhydrazine --> colon ◦Xenografts–implanted tumours in nude mice/rats
38
How to study nutrition and lifecycle? What are the limitations?
• Does diet have an impact on the ageing process? The speed? • Difficult to study in humans (lifespan 80 years) ◦--> Animals with shorter life span • Example: Developmental origins of health and disease ◦Early evidence from retrospective epi studies ◦Biological plausibility; mechanisms: animal studies ◦Examples
39
What does biological plausibility mean?
most research is from epi studies and we have theories that we can test on animals. Once we are able to explain it on animals how the physiology works then we are having biological plausibility.
40
Explain the animal models of aging
* Regardless of chronic disease risk, can diet affect life span? * Rats fed nutritionally adequate but energy-reduced diet * average and max life span extended * delay of many age-related diseases * Shown in rats, mice, hamsters, flies, worms, yeast * Other studies in non-human primates–inconclusive
41
Important considerations for nutrition research on animals
• Choice of species • Experimental design ◦Dose of a nutrient ◦Form in which nutrient is delivered ◦E.g. chemically extracted phytonutrients from plant material •Bioavailability or metabolism •Gut microflora (different in animals than humans)

NUTR 606 Research Methods (6 decks)

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