Lecture #19 ~ Intro to Lab Animals

Dr. Uzumcu

what is responsible for increasing life expectancy between 1890 and 1950?

health improvements in YOUNG population (i.e. childhood vaccines)

What is responsible for increasing life expectancy between 1950 and 2010?

Health improvements in OLDER population (i.e. heart disease treatment)

Define lab animal

Any animal used in biomedical research, testing, and teaching

Most commonly used species as lab animals are:

mice, rats, fish, birds, rabbits, hamsters, non-human primates, dogs, etc.

Number of animals used in research in the US in 2010

26 million

Number of animals used in research in the UK in 2013

4.2 million

Number of animals used in research around the world in 2013

100 million

~___% of these animals used in the US are mice, rats, fish, and birds

96

Defie Laboratory Animal Science

The Science and tech dealing w/ the procurement, breeding, care, health, and selection of animals used in biomedical research and testing

Components of lab animal science:

lab animal care and medicine, animal experimentation

What were some major medical advances in the 19th century?

vaccines, anesthetics, surgical techniques, and infection prevention techniques

Who was Alex Carrel?

French surgeon and biologist awarded Nobel Prize in Physiology and Medicine in 1912 for work on vascular suture and transplantation of blood vessels and organs (learnt from animal experimentation)

What were advances in 20th century?

chemistry, radiology, pharmacology, genetics, immunology, and molecular biology

When was the beginning of modern lab animal science

1950

Five Chicago-area vet organized what in 1950

1st national meeting of the Animal Care Panel (now American Association for Lab Ani Sci)

AVMA considered Lab Ani Medicine as__ in 1957?

Separate discipline

What are the two main ethical concepts?

Right-based vs. consequentialist ethics

What are the two opposing views?

Animal rights vs. animal welfare

What does knowledge gained to benefit humans justify?

Animals being used in an ethical manner

In which opposing view do certain rules need to be followed ?

Animal welfare

What is at the foundation of these “certain rules”?

Three Rs Principles

What are the 3 Rs?

Replacement, reduction, refinement

Describe replacement

Replace higher vertebrates w/ lower or non-animal models (animal alternatives)

Describe reduction

Reduce animal numbers to optimal optimum number

how ot find optimal optimum number?

Statistical analysis and preliminary studies

Describe refinement

Refine research procedures to minimize pain and suffering of procedures

Examples of tools used in refinement

Anesthetics during and analgesics after surgery

Examples of medical advances for animals from animal research

Longer/healthier lives, better understanding of nutritional sciences, vaccines for well-being of companion anis

_____ has been and continues to be one of the fundamental approaches to the scientific method in biological and medical research and education, leading to major discoveries in biomedical sciences

animal research

Examples of discoveries: COVID-19 + vaccine ; describe

Preclinical data w/ Modernas mRNA vaccine produced promising results in animal models

Examples of discoveries: Insulin

1920-22, Canada, Dr. Banting + Prof Macleod, dogs and cattle, insulin allows for longer normal life

Examples of discoveries: “The Pill” and IVF-Embryo transfer

Pill (1960, US) = Dr. Pincus and Min Chueh Change, using rabbits; IVF baby (1950-78, England) = Dr. Edwards and Steptoe, using mice

True or false: the care and use of lab animals in research are highly regulated

True; it’s regulated by local, state, and federal laws

Name the layers of federal oversight

A. Animal Welfare Act (AWA)

B. PHS Policy on Humane Care and Use of Laboratory Animals and the Guide

C. Other Federal Regulations

true or false: individual states may regulate the care and use of animals for research

true (example = Massachusetts)

How can there be more local control over animal research?

Municipalities can also have laws and regulations

Describe Animal Welfare Act

Protects all warm-blooded animals except rats, mice, and birds; enacted 1966 to cover transport/sale/handling of animals and provide licensing, USDA enforced via lab inspections and monitoring compliance, amended often

When was the most important amendment to the AWA and describe it

1985 - Improved Standards for Lab Ani Act + establishment of Institutional Animal Care and Use Committee (IACUC)

Describe The Public Health Service Policy

Covers species common species not covered by AWA, such as live vertebrates (like fish and reptiles), based on Health Research Extension Act in 1985, applies to any research facility that receives NHS funds (including NIH grants), researchers must follow the Guide, each facility must maintain IACUC and report whether they are accredited

Describe the Guide

Published in 1963 by Animal Care Panel (later the AALAS), not published by Institute for Lab Research of NRC (part of NAS), central piece of the Policy, enforceable and forced by NIH OLAW, periodically updated w/ humane and scientific standards, basis for AAALACi accrediation

Describe IACUC

Functions to review all proposed animal experiments, inspect animal facilities twice a year, and provide oversight of welfare of animals in their institution; composed of 5 members

Who are the five members in IACUC

DVM responsible for animal care at the institution, scientist, member who isn’t affiliated w/ the institution, pro whose primary concerns are not scientific

Describe AAALAC International

Founded in 1965 to promote uniform standards of animal care in US labs on a voluntary basis; assess accredits research facilities all around the world

Describe the Good Laboratory Practices (GLP)

Governs the FDA and EPA regulations; governs care and use of animals that are used during preclinical studies; noncompliance = consequences from study rejection to lab disqualification

What does the FDA oversee

Any new drug development which involves preclinical animal studes

Describe AALAS (established as Animal Care Panel in 1950)

Concerned w/ production, care, and study of lab animals; 10k members, 49 branches, 19 affiliates; pro org. that brings together individuals or institutions w/ interest in lab ani sci; produced educational materials, publishes journals, provides certification

Describe National Association for Biomedical Research

Foster framework for animal use acceptable to scientific community and the public

Describe American Veterinary Medical Association

Organization for vets

Describe American College of Lab Animal Medicine

Vets specialize in lab ani medicine

Describe People for the Ethical Treatment of Animals

Against the use of animals in research

What was the first mammalian domesticated for scientific purpose

Rat

What is outbred

Genetically variable

What is inbred

Genetically identical

What studies are rats used for in labs

Nutritional and behavioral studies

true or false: both outbred stocks and inbred strains of rats are used

true

Unique features of rats:

Don’t vomit

Don’t have canines or premolars (one pair of upper and lower incisors and three upper and lower molar on each sides)

Malocclusion is common in those that don’t gnaw (should be treated)

Tears contain porphyrin = stress/pain

How are rats commonly fed and w/ what?

Ad libitum; commercially available diets/chow unless required otherwise

When do rats reach sexual maturity

5-8 weeks for males and females

describe the outward sign in rats

vaginal opening in females and testicular descend in males

when is the first estrus in female rats

5 weeks

true or false: rats are spontaneous ovulators

true

what is important for maintenance of corpora lutea in rats?

vaginal stimulation

How long does estrus last for rats?

12 hours every 4-5 days

When does female fertility in rats decrease

20-22 months

When does rat male fertility decrease

16-20 months

When is maximal fertility for rats

100 - 300 days

Males rat mount and ejaculate several times in ______ min

15-20

In rats, Gestation varies ….

19-23 days (mean 21-22 days)

When does semen coagulate and form vaginal plug in rats

At night

Rat Monogamous pairs - takes advantage of __

postpartum estrus (shortly after birth)

most common in rats = 

polygamous breeding (1 male, 6-9 females)

light:

dark cycle 12-16 hr. light / 24 hr - best ???

rat litter average #

8-14 pups

Neonate weight of rats

5-6g

Describe why rats are altricial

hairless, blind, closed ears, undeveloped limbs, short tail

When do rat ears open

2.5-2.5 days

when do rat incisors erupt

8-10 days

when do rat eyes open

12-16 days

when are rats fully haired

7-10 days

when do rats wean

21 days

how much do rat adult males weigh

300-400 g

how much do rat adult females weigh

250-300 g

true or false: rats are nocturnal

true

What is the most commonly used mammal

mouse

in which fields are mice commonly used

immunology, oncology, microbiology, biochem, etc.

how much are mice fed a day

3-5g feed

how much water do mice drink per day

6-7 ml

why are mice susceptible to environmental changes?

large SA to body weight ratio

mice have a ___ turnover of body water

rapid

what is the thermoneutral zone for mice

29.6 - 30.5 degrees C (VERY NARROW)

what happens if a mouse has lower than thermoneutral temp?

increased tumor growth bc of immune suppression

when do female mouse cycles begin

30 days

when do males reach puberty in mice

44 days

how long is estrus cycle in mice

4-5 days

how to follow the cycle days in mice?

vaginal changes

when is postpartum estrus

14-24 hr

lactational delay of implantation prolongs gestation ___ days

12-13

mating occurs in ___ phase

dark

how long is mouse gestation

19-21 days

when are mice weaned

21 days