The Mouse
BACKGROUND
The mouse is a mammal classified in the order Rodentia, suborder Sciurognathi. There
are three major families of mice: Muridae, Cricertidae, and Platacanthomyidae. The
taxonomic name for the laboratory mouse is Mus musculus. It is also the name of the
common house mouse which has been domesticated. Mice are originally from Europe,
but have been spread world-wide by humans. Many decades of breeding for specific
characteristics have provided a vast array of genetic variants that are well characterized
anatomically & physiologically. For this reason, the mouse has been extensively used in
research since the early1800s. Research uses include immunology, toxicology, cancer
pharmacology, behavior, and infectious disease.
FYI: There are a large number of strains with various known genetic backgrounds. These
differences in genetic variations have long been used as the foundations for all types of
experiments. Transgenic and knockout strains are starting to replace many of the
traditional mouse strains.
o
Inbred strains, such as the Balb/C, or C57BL/6 are animals that are genetically identical
because of extensive mating between siblings and parents. They are used to reduce
experimental variability between animals.
o
Outbred strains, such as the Swiss-Webster or ICR, are genetically diverse within a
strain, but the genetics of a strain is maintained as a constant. These animals are often
used for studies where genetic variability either is not important or is desired.
BEHAVIOR
Mice are timid, social, and territorial animals. When handled properly, mice are rarely
aggressive. They tend to be quite curious and may become adept at escaping their
enclosures. They have very acute hearing and a well developed sense of smell. Their poor
vision makes them unable to detect color, so red lights are often used to observe these
animals during their normal nocturnal cycles.
* Mice that are group housed often develop a social hierarchy, especially males.
The dominant animal can cause extensive wounds to the back, tail and genital
region of submissive animals in the cage. Therefore, male mice should never be
housed together because of their tendency to fight which results in dermatitis,
abscesses, septicemia, and even death.
* Mice in the wild are primarily nocturnal [active at night], but laboratory and pet
mice are alternately active and resting throughout the day and night.
* Mice groom themselves and each other extensively. Over-grooming by a
dominant mouse may result in hair loss. This is called barbering.
Housing and Nutrition
Mice are usually housed in solid-bottom shoe-box style cages. Mouse cages should
provide at least 97 cm² [15 in²] floor space per adult [30 g] mouse and be at least 13 cm
[5 inches] high.
Bedding for these cages must be absorbent, dust free, unpalatable, insulating, and free of
infectious agents. Corn cobs, cellulose, or wood shavings are commonly used. Mice
often create nests from bedding material and shredded paper may be provided for this
purpose. Cages should be cleaned at least three times weekly and new, dry, clean bedding
provided.
Fresh, potable water must be available at all times. Water consumption is approximately
15 ml per 100 g body weight per day and should be changed at least 3 times per week.
Feeding requirements vary with different species of mice. The common Swiss mouse
normally consumes 12 to 18 g [15 g average] per 100g body weight per day. The best
feed for rodents is the high protein [over 14%] “hamster and gerbil” feed. This pelleted
commercial rodent chow is adequate and can be fed from the V-shaped trough in the wire
cage lid. Coprophagia is an important component of mouse nutrition. Sweets, treats,
vitamins, salt blocks, and vegetables are NOT necessary and may lead to illness.
The ideal ambient temperature is between 18° to 29º C (65° and 85° F) with a relative
humidity of 40% to 70%. Mice can be acclimated to cooler temperatures.
Cage enrichment is also important. To enhance the environment, any nontoxic item that
mice can gnaw will be useful.
Handling and Restraint
Specific handling and restraint techniques vary depending on the purpose of the
manipulation. When removing the lid from the cage for access to the mice, it is
important to remove the water bottle to prevent spillage.
When handling mice, it is advisable to wear gloves to prevent development of allergies
due to contact with animal dander and urine. A mask may also be worn to prevent
inhalation of dust or aerosols.
1. Gentle handling is always the best. Frequent handling will acclimate the animal to
people and these mice can be easily moved.
2. Animals may be scooped up into both hands in order to transfer them to another cage.
The drawback with this method is lack of control due to the curiosity and speed of the
mouse. If attempting to escape, it is possible that injury to the mouse could result if the
animal jumps or falls to the ground. Other injuries could occur when trying to grab the
animal as it tries to evade capture. However, well handled animals prefer the hand scoop
method of handling and normally don’t try to escape.
Some animals will attempt to bite your hands or consistently jump from them.
For these animals, use a plastic beaker or other container.
3. Due to their long tails, mice may be lifted by the tail near its base using your thumb
and forefinger. Support the body of the mouse by your other hand or sleeve. This is
especially important when handling obese or pregnant mice.
Do not grab the tail beyond the midpoint region and never grasp near the tip of the tail
because the skin may slough and leave exposed vertebrae. Never allow the animal to
dangle by the tail. If this happens, the mouse will nearly always climb up its tail and bite
the handler. If the animal tries to turn around and bite, slowly turn the tail rotating the
animal to keep it off balance.
Likewise, smooth, rubber tipped forceps may also be used to lift the mouse by the body
or to grasp the skin across the back of the neck.
When returning mice to their cage, the animals should be lowered and released upon
contact with the bedding to avoid being dropped into the cage which could result in
spinal fractures.
4. Most rodents may be handled by the scruff of the neck for restraint for other
procedures. It is best to let them stand on a flat surface, with either something for them to
grip on with their front feet only (the cage top) or on something smooth. Then grasp the
scruff and pull up as much skin as possible to hold them securely. Don't take so much
skin that they have difficulty breathing.
5. Investigators frequently use restraint devices if animal must be handled for a period of
time, or anesthesia if a painful procedure will be performed.
Normal Physiological Reference Values for Mice
Average Life span
12-36 months
Gestation
19-21 days
Average Litter size
7-11 cubs
Average adult body weight
Males [Bucks]: 20-40 g
Females [Does]: 22-63 g
Body surface area
For a 20g mouse, BSA = 36 cm²
Formula: 10.5(wt. in grams) 2/3
Body temperature [rectal]
36.5° C -38.0° C
Respiratory Rate [breaths per minute]
80-216 /min
Tidal Volume
0.09-0.23 ml
Oxygen Use
1.63-2.17 ml / g/ hr
Heart Rate [beats per minute]
325-780 /min
Blood Volume
76-80 mg/ kg
Blood Pressure
113-147/81-106 mm Hg
Public Health Concerns
A. Cutaneous and respiratory allergies to rodent dander
B. Zoonosis
i. Salmonellosis : Gram negative bacteria causing diarrhea.
ii. Lymphocytic Choriomeningitis (LCM):
Arena virus
Various forms in rodents:
Cerebral: neurological signs, death
Visceral: variable signs
Mode of transmission:
animal (murine) cell lines primarily
rarely via urine or feces
Human Disease: Mild-flu like symptoms
iii. Rat Bite Fever (Haverhill fever)
Streptobacillus moniliformis
Rodent host is asymptomatic, organism in oral cavity and upper
respiratory tract
Mode of transmission:
Bite of carrier rodent
Human Disease: Inflammation at site of bite, lymphadenopathy, malaise.
Untreated complications include: arthritis, pneumonia, hepatitis,
pyelonephritis, enteritis, and endocarditis.
iv. Hantavirus
Bunyavirdiae
Specific rodent host can harbor specific Hantavirus, named for region
Asymptomatic in rodent host, will remain persistently infected for life
Mode of Transmission:
Inhalation of aerosols or dust from bedding containing
contaminated saliva or excrement.
Human Disease
Varies per strain
U.S.: pulmonary syndrome = pulmonary edema, respiratory failure
CCCCD Lab Animal Care Conventional Rodent Care for lab staff:
∗ Feeding, watering, and changing cages for mice. Gloves should be worn at all times
when handling mice or when cleaning and changing cages. Masks may also be used.
∗ Observing mice daily to ensure they are eating and drinking. If not, or if they appear to
be ill, contact the lab director. More common illnesses that may be observed include
those related to the following systems: skin [hair loss, swellings, dermatitis]; GI
[diarrhea, weight loss]; respiratory [nasal discharge, dyspnea]; neuromuscular [head tilt,
convulsions, trauma, death]
* Animals will be housed in the prep area during the week of the respiratory metabolism
experiment. At the end of classes each day, the mice are to be returned to the prep area.
Lights in the prep room should be turned off before leaving.
* Healthy animals will be returned to the pet store upon completion of the respiratory
metabolism experiments.
* Unhealthy or injured animals will be examined by qualified personnel. Any medical
decisions regarding treatment or disposal shall be made upon consultation with a
veterinarian.
Further Research about Laboratory Animal Use
Regulatory Agencies
A. National
1.
The United States Department of Agriculture (USDA) regulates all warm-blooded animals, except
rats, mice and birds, used in biomedical research, exhibition, and teaching, as well as breeders
through a set of laws known as the Animal Welfare Act
2.
The United States Public Health Service (PHS) regulates all vertebrates used in research, testing
and training in projects that receive money from that agency. This includes grants received
through the National Institutes of Health (NIH) as well as others. A general set of guidelines
known as the US Government Principles for the Utilization and Care of Vertebrate Animals Used
in Testing, Research, and Training form the framework for PHS regulations. More specific
guidelines are detailed in the Guide for the Care and Use of Laboratory Animals.
3.
The Association for the Assessment and Accreditation of Laboratory Animal Care, International
(AAALAC) is an agency that assesses the quality of the animal care program and facilities. This
program is voluntary on the part of the institution. AAALAC utilizes the guidelines in the Guide
for the Care and Use of Laboratory Animals as standards for quality of animal care.
4.
Other agencies, such as the Food and Drug Administration and the Department of the Interior
regulate specific activities and animal usage.
B. University
1.
The University of Minnesota Board of Regents Policy and Procedures for Animal Care and Usage
specifies guidelines for all vertebrate animals used at the University, similar to those put forth by
the PHS.
2.
The Institutional Animal Care and Use Committee (IACUC) is responsible for review of all
animal use protocols and facilities for animals used at the University of Minnesota, including
outlying campuses. Investigators may only perform procedures detailed in their approved Animal
Usage Form (protocol). If there are concerns that this is not the case, the problem should initially
be referred to your supervisor, who will contact an RAR veterinarian to investigate the problem
and inform the IACUC if there is a violation. You may also report suspected animal welfare
violations directly to the IACUC at 626-5654.
3.
Research Animal Resources is the department given the responsibility for caring for animals used
in the Academic Health Center and the College of Liberal Arts, and for providing veterinary input
to the IACUC for all animal use at the University of Minnesota.
III. What do the Regulations Say?
The regulatory documents for animal care and use are very extensive. Anyone interested
in reading them may request copies from the Veterinary Services office (B305 PWB, 49100) or can obtain them from the RAR website. A summary of the basic principles are
below.
1.
Husbandry- Specific guidelines are given for transportation, cage sizes and configuration,
cleaning and sanitation. Living conditions should be tailored to the needs of each species.
2.
Experimental goals should be relevant to human or animal health, the advancement of
knowledge, or the good of society.
3.
The animals selected for procedures should be of an appropriate species and quality, and the
appropriate number required to obtain valid results. Alternatives such as mathematical models,
computer simulation, and in vitro biological systems should be considered.
4.
All procedures must be designed and performed to minimize pain or distress to animals.
o
Unless the contrary is established, investigators should consider that procedures causing
pain or distress in humans may cause pain or distress in other animals.
o
Distress is defined as expression of maladaptive behavior or the inability to adapt to
environmental change.
5.
Procedures with animals that may cause more than momentary or slight pain or distress should be
performed with appropriate sedation, analgesia, anesthesia, or this should be relieved by
euthanasia.
6.
Experimental endpoints should be defined and adhered to. A veterinarian or other scientist
trained and experienced in the proper care, handling, and use of that species must be in charge of
the animal care program. Adequate veterinary medical care must be provided when needed.
7.
Training- Investigators and other personnel shall be appropriately qualified and experienced in
the proper care, handling, and use of the species being maintained or studied.
8.
Animal use protocols are reviewed by a committee, which includes at least one scientist, a
veterinarian, and a member of the public. Where exceptions are required, they must be granted by
the committee, not just the investigator, and should be made for scientific purposes, not solely for
the purposes of cost savings, teaching or demonstration.
References
The Biology and Medicine of Rabbits and Rodents. John E. Harkness and Joseph E.
Wagner
Laboratory Animal Medicine: Principles and Procedures. Margi Sirois
http://www.nap.edu/readingroom/books/labrats/contents.html
[A print out of the above web site chapters Guide for Basic Care and Use of Laboratory
Animals] is available in a spiral notebook in the SCC prep room.
http://research.uiowa.edu/animal/?get=mouse
http://www.ehs.ucla.edu/AH_ZRodents.html