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. 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 cm [15 in] 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 29 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 dont 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 Gestation Average Litter size Average adult body weight 12-36 months 19-21 days 7-11 cubs Males [Bucks]: 20-40 g Females [Does]: 22-63 g Body surface area For a 20g mouse, BSA = 36 cm Formula: 10.5(wt. in grams) 2/3 Body temperature [rectal] Respiratory Rate [breaths per minute] Tidal Volume Oxygen Use Heart Rate [beats per minute] Blood Volume Blood Pressure 36.5 C -38.0 C 80-216 /min 0.09-0.23 ml 1.63-2.17 ml / g/ hr 325-780 /min 76-80 mg/ kg 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 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. 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. Other agencies, such as the Food and Drug Administration and the Department of the Interior regulate specific activities and animal usage.

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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. 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. 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.

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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.

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Experimental goals should be relevant to human or animal health, the advancement of knowledge, or the good of society. 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. All procedures must be designed and performed to minimize pain or distress to animals. o 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. Distress is defined as expression of maladaptive behavior or the inability to adapt to environmental change.

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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. 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. 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. 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.

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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