Past Role Of Laboratory Animals

Any attempt to assemble a comprehensive or detailed chronological overview of all the contributions to biomedical research that are based on experiments involving laboratory animals would result in either an endless list or a vast volume of medical accomplishments, and would be neither complete nor useful. However, the Foundation for Biomedical Research has compiled a list of Nobel Prize winners from the year 1901 to the present this includes 67 examples, ranging from determinations of basic...

Diabetes Assessment

Diabetes affects millions of people worldwide. It is a leading cause of death, and as a result, is a large area of study. Diabetes is actually a group of diseases characterized by aberrant glucose metabolism. Type I or insulin-dependent diabetes results from immune-mediated destruction of pancreatic beta-cells. Type II or noninsulin-dependent diabetes results in hyperglycemia without loss of endogenous insulin reserve or loss of pancreatic islets. Thus, Type II diabetes is characterized by the...

The Development Of Laboratory Animal Genetics

The remarkable advances in the science of genetics over the past few decades are having a strong impact on laboratory animal science. These advances are due to the development of a range of molecular techniques making it possible to map, clone, and sequence many genes, but progress has been facilitated by the classical period of mouse genetics which started soon after the rediscovery of Mendel's work in 1900 and continued until about 1980. This laid a firm foundation on which the new molecular...

F1Hybrids

These are the first-generation cross between two inbred strains, and being isogenic, they have many of the more useful properties of the parental inbred strains. They also usually exhibit hybrid vigor, which means that they are more vigorous than inbred strains and are less influenced by adverse environmental conditions. As a result, they tend to be slightly more uniform than inbred strains.39 However, they may also be less responsive to experimental treatments, so the increased uniformity does...

Health Surveillance

Surveillance for health quality is essential to detect unwanted and complicating spontaneously occurring mouse diseases. Health monitoring entails sampling of sentinel mice in the quarantine areas as well as any SPF mice in the colony. This can be done at intervals of 4 weeks in the quarantine area and every 12 weeks in the repository colony. Sentinel mice are often SW, 2-month-old females. These mice are free of all the agents that will be screened. In the barrier colony, sentinel mice are...

References

Rossant, J. and McKerlie, C., Mouse-based phenogenomics for modeling human disease, TrendsMol. Med, 11, 502, 2001. 2. Moldin, S.O. et al., Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis, Mamm. Genome, 8, 575, 2001. 3. Mahner, M. and Kary, M., What exactly are genomes, genotypes, and phenotypes And what about phenomes , J. Theor. Biol., 1, 55, 1997. 4. Osman, G. et al., SWR an inbred strain suitable for generating transgenic mice, Lab. Anim. Sci., 2, 8, 1997. 5. Ladiges,...

Respiratory Protective Equipment

Half-face particle filter respirators are a significant control measure used in successful programms.12,23 Such respirators of type P2 have been shown to reduce inhaled allergen by 90 .59 This should be sharply contrasted with the disposable surgical masks that are occasionally used. These are primarily designed to protect surgical fields from exhaled droplets. They provide a poor seal around the edge and, although they may be comfortable to wear, provide limited, if any, protection. Several...

Vaccination

If all other measures are unsuccessful or impossible to apply, the use of animals protected by vaccination may be considered. If vaccination is unavoidable, one should in the first place consider whether it might be sufficient to vaccinate the female breeding animals only, as passive immunization through maternal antibodies in most cases must be considered as less interfering with research than active immunization of the experimental animal. Apart from this, it is easier and cheaper. In this...

Staphylococci

Staphylococci are found worldwide in all species of animals and are spread between species, including animal to humans and vice versa. The majority of humans and animals are carriers of staphylococci. Staphylococcus aureus is found with a high prevalence in most colonies of laboratory rodents2 as well as in most humans, while in wild mice, S. aureus is rather uncommon. Other types of Staphylococci common in laboratory rats and mice include S. haemolyticus, S. xylosus, S. sciuri, and S....

Learning and Memory Assessment

The Morris water task is one of the most widely used paradigms to evaluate learning and memory behavior. This is a spatial navigation task in which the mouse swims to find a hidden platform, using visual cues to locate the platform. Escape from the water is the positive reinforcement. The task is based on the principle that mice are highly motivated to escape from a water environment by the quickest, most direct route. The procedure requires a circular plastic tank about 30 cm in diameter and...

Consomic or Chromosome Substitution Strains

Definition, Development, and Research Uses Consomic strains are developed by backcrossing a whole chromosome from one donor inbred strain into a recipient background strain. They are used for studying the genetics of complex traits and in the eventual identification of QTLs.51 A minimum of ten backcrosses should be used, though ideally, all the background strain chromosomes should be present and uncontaminated with donor chromosomal fragments (with the exception of the donor chromosome). The...

Cardiac Assessment

As heart disease in western society and around the world becomes more conspicuous as a source of illness and death, so do genetically engineered mice designed to facilitate the study of the cardiovascular system and the effects of specific genes on its various failings. Methods to assess the cardiovascular system are varied in their complexity and versatility. Investigators should carefully select those testing techniques best suited to the specific genes and questions being addressed. In all...

Tumor Assessment

Transgenic mice have long been an important resource for studying human neoplasms, both benign and malignant. In addition to the numerous genetically engineered mouse models developed over the years, many popular background strains have a genetic predisposition toward certain types of tumors. Knowing the effect of the background strain is important in research involving genetic manipulation with genes involved in tumor pathways. In addition, a detailed understanding of the biochemical cycles...

Herpesviruses

Cytomegaloviruses are also known as salivary gland viruses. Several species-specific strains exist, among these, strains infecting mice, rats, and guinea pigs. Megalic cells and nuclear inclusions in the glandular epithelium of the salivary glands characterize infection. Infection is rare in laboratory colonies. Mouse thymic virus infects only mice, in which it may be found in the thymus and the salivary glands. Infection with mouse thymic virus is occasionally reported in laboratory mouse...

Congenie and Coisogenic Strains

A pair of strains is said to be coisogenic if they differ at only a single genetic locus as a result of a mutation within one branch of the strain. Such strains are useful, because the effects of the mutation can be studied without the complication of genetic segregation in the genetic background. Unfortunately, coisogenic strains cannot be produced to order, as they depend on the mutation occurring within the inbred strain, which is uncontrollable. However, targeted mutations produced by...

Pulmonary Function

There is increasing interest in the use of genetically engineered mice in inhalation toxicology studies involving host variables, including genetics, age, diet, and disease.28 This interest derives from epidemiology that suggests an association with air pollution-related human mortality morbidity, especially among individuals with cardiopulmonary disease. Several mouse models with genetically based cardiopulmonary diseases are now being incorporated into inhalation toxicology studies to...

Bone Density Assessment

It is important to evaluate and compare bone mineral densities in various aging mouse cohorts and for any study that attempts to show the effect of any type of treatment on bone. Trabecular bone density can be measured by three established methods. These three methods include trabecular bone volume by histomorphometry (BV TV ), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular bone by duel-energy x-ray absorptiometry (DEXA)....

Colony Phenotyping

The objectives of phenotyping procedures are to cover the basics of observational assessment, gross necropsy examination, whole body and individual organ weights, clinical pathology assessments, and histological examination. As a first step in phenotyping mutant mouse lines, assessment of the colony as a whole unit is an important aspect. All mice should be observed at birth and at least once a week from birth until that time when the individual mouse is used for an experiment, euthanized, or...

Administrative Training and Personnel Health and Hygiene

Managing an animal facility is a complex business that requires the coordinated effort of a variety of staff, many of whom require office space, including professional, management, supervisory, training, and clerical staff. It is highly desirable to provide the administrative and training space in a consolidated suite adjacent to the animal facility but outside of the security perimeter. The suite should include space for office equipment and storage of office supplies and files and amenities...

Respiratory

Comparison of symptoms in LAA subjects ( ). (Aoyama, K., et al., Br. J. Ind. Med., 1992 49 41-47. Reproduced with permission.)29 Immunological tests are valuable, as they provide additional confirmatory evidence of the diagnosis. The most widely used tests are skin-prick tests and immunoassay tests for specific IgE in the serum. In skin-prick testing, an extract of allergen is placed on the skin and the underlying skin is then punctured. The skin reaction is then compared with a...

The Ethical Dilemma

Behind questions such as these lies an ethical dilemma. Ordinarily, when we describe someone as facing a dilemma, we mean that the person is in a no-win situation whatever he or she does, the result will be unsatisfactory in some way. An ethical dilemma is a special case of this. It again involves a no-win sit * Questions like these are examined at greater length at the end of the section entitled Claim (1) The Need for Animal Research. uation, but this time, whatever the person does, the...

Info

Preventing Asthma in Animal Handlers (NIOSH 1998)78 Preventing Asthma in Animal Handlers (NIOSH 1998)78 Perform animal manipulations within ventilated hoods or safety cabinets when possible. Avoid wearing street clothes while working with animals. Leave work clothes at the workplace to avoid potential exposure problems for family members. Keep cages and animal areas clean. Reduce skin contact with animal products, such as dander, serum, and urine, by using gloves, lab coats, and approved...

Engineering Controls

Animal facilities should be designed to incorporate engineering controls to the extent feasible. The most likely limitations to the introduction of engineering controls are the constraints imposed by the existing facility and the need for significant capital investment. In existing facilities, the costs of retrofitting may be prohibitive, not least because to do so may mean business operations have to stop temporarily. One of the problems associated with evaluating engineering controls is that...

Necropsy Procedure

Initial characterization should include necropsies performed on immature and mature mice of both genders as well as mice sacrificed in a moribund condition or found dead (autolytic state permitting). Embryos and fetuses should be examined in those mouse lines with high fetal loss or developmental anomalies. Blood for serum chemistry evaluation should be collected immediately before euthanasia. The necropsy is performed in a systematic and orderly fashion. Tissues in each system are evaluated...

Future Directions For Laboratory Animals In Biomedical Research

Genetically Engineering Technologies (see also Genetically Altered Mice) As we have seen, the genomic revolution has opened new and seemingly unlimited possibilities for biomedical research. Reading and understanding the genomic blueprints associated with specific pheno-types, including pathologic or advantageous characteristics, provide the possibility of intervening at the gene level in certain disease conditions. This contrasts with the traditional approach of treating signs of illness and...

Skin Assessment

One of the most common organs to study is the skin. It is relatively easy to examine and identify phenotypic variations which can become an important resource for gene-targeting studies. When evaluating the skin and coat, it is important to keep in mind that phenotypes can vary dramatically. Some mutations have no obvious effects, whereas others can dramatically change the appearance of the mice. Problems with the skin and coat can be due to environmental problems, parasites, autoimmune...

Clinical Manifestations

Symptoms during work with laboratory animals are mainly, but not exclusively, mediated by mechanisms initiated by the interaction of allergen with specific IgE. Symptoms of LAA arise from the release of biochemical mediators that lead to an inflammatory response. The nature of the symptoms vary from person to person, but form three principal patterns that affect the nose and eyes, chest, and skin. The most commonly reported symptoms affect the nose and eyes (rhinitis and conjunctivitis). The...

Integrated Health Safety And Welfare

It is imperative that efforts to reduce staff exposure to animal allergens with the goal of reducing incidence of LAA do not give rise to new health problems, either among staff or animals. If allergen levels are reduced, but with increased ergonomic strain and compromised animal welfare (potentially affecting research), nothing has been gained. Few studies have as yet focused on these balances. Recently, cage systems for containing mice were compared, evaluating allergen levels, ergonomics...

The Editors

Jann Hau is Professor in Comparative Medicine at University of Uppsala in Sweden. Dr. Hau graduated in experimental biology from University of Odense in Denmark after medical and biology studies in 1977, and specialized in laboratory animal science. Following research fellowships at University of Odense, he did his doctorate (Dr. Med) at this university. In 1983, he joined the Department of Pathology at The Royal Veterinary and Agricultural University (RVAU) in Copenhagen as Associate Professor...

Asia

In Japan, the Prime Minister's Office is responsible for animal-protection laws and regulations. Although animal protection in Japan is based predominantly on ethical principles (derived in large part from their Buddhist traditions), the Law for the Protection and Management of Animals (1973, translated into English in 1982)19 and the Standards Relating to the Care and Management of Experimental Animals (1980)20 are the framework for animal care and use for all universities and public and...

Colony Assessment

It is essential for accurate phenotypic characterization that the integrity of the genetic alteration of a specific line be maintained over several generations of backcrossing using sound breeding practices and accurate record keeping. In addition, basic observational assessments at the colony level to detect any unusual characteristics of newly generated mouse lines are mandatory in research involving genetically engineered mice. An important strategy in validating and maintaining the...

Scope

Animals maintained as microbiologically defined according to rederivation and containment principles described above, should be regularly controlled to confirm this status. Therefore, a number of animals Figure 11.13 Examples of test performed on each sampled animal in health (microbiological) monitoring of rodents. Figure 11.13 Examples of test performed on each sampled animal in health (microbiological) monitoring of rodents. are sampled from the colony at frequent intervals and are subjected...

Introduction

Laboratory animal allergy (LAA) is a common health problem in biomedical research and the prevalence of allergy has been found to be as high as 56 of animal-exposed workers.1 Sensitization to laboratory animal allergens can give rise to both severe, acute (anaphylactic) reactions2 and disabling chronic illnesses (dermatitis and asthma). Both acute and chronic reactions to allergen exposure can have a significant adverse impact on affected workers and their employers. Several authors have...

Embryo Transfer

As an alternative to cesarian section, embryo transfer has been used over the last 20 years. The advantages to cesarian section are that the embryos may be kept for long periods in liquid nitrogen and used for further rederivation whenever needed. The technique is also a must for the production of transgenic Donor females Recipient females Donor females Recipient females Figure 11.5 Principles of embryo transfer. Figure 11.5 Principles of embryo transfer. animals. Disadvantageous is that more...

Pre Placement Assessment Assessing Risk

The prevention of allergy should begin before exposure to allergen occurs. Assessment of potential animal workers prior to commencing work with animals is good practice, and also a legal duty in some jurisdictions. Partly, the purpose of this assessment is to consider individual vulnerability to allergy. It is also to consider the worker's capability to do the proposed work and determine the need for interventions and adjustments (such as immunization against infectious diseases and provision...

North America

There is no federal legislation pertaining to the use of animals in research, testing, or education in Canada. However, some provinces have established provincial laws, and there is a voluntary assessment program for the care and use of experimental animals. In addition, although there is no federal requirement to participate in the Canadian Council on Animal Care (CCAC) assessment program, some funding agencies require grantee institutions to comply with CCAC guidelines, and contractors...

Utilitarianism

According to the utilitarian, the interests of every individual affected by an action count morally and deserve equal consideration. In utilitarian writings, the notion of an interest is usually defined in terms of the capacity for suffering or enjoyment or happiness.21 Thus, individuals have an interest in acts that will enhance their enjoyment or reduce their suffering. From this it follows that all sentient beings, human and nonhuman, have interests. And, since for the utilitarian, all...

Special Sensory Assessment

Assessment of the special senses allows for evaluation of cranial nerve function as well as normal structure and function of the eyes, ears, and brain. In some cases, a known phenotype for a specific transgene is the loss of visual or auditory acuity early in the life span. In others, a slight change in brain and cranial nerve structure or in development can have large affects on the ability of the genetically engineered mouse to hear and see normally from birth. Detection of changes in these...

Immune Function Assessment

Phenotypes of genetically altered mice can be validated and enhanced by conducting basic immune function assays. These assays provide information to distinguish whether phenotypic characteristics are associated with secondary changes and ill health, or are the direct or indirect result of genetic manipulation. Basic immune analyses provide further evidence of the validity of these observations. In addition, novel phenotypes can be identified for understanding molecules and pathways involved in...

Mutants Polymorphisms Transgenic and Gene Targeted Mutations Collectively Known as Mutants

Several thousand mutants, polymorphisms, and transgenes of various sorts are now used in biomedical research, and the numbers will increase substantially over the next few years as targeted mutations and mutants produced by chemical mutagenesis continue to be produced. These have a Mendelian mode of inheritance, though there may be complications due to variation in gene expression, penetrance, viability, and breeding performance. The spontaneous or induced mutations and polymorphisms may be...

Lean Body Mass

Muscle wasting is a consequence of many systemic diseases such as diabetes, cancer, sepsis, hyperthy-roidism, uremia, muscle disuse, and nerve injury. Thus, muscle mass determination is important to many systemic disease studies. Muscle-specific phenotyping procedures are important and consist of an intensive anatomic evaluation that involves muscle mass determination via gross pathology and histology, followed by biochemical techniques such as molecular flux spectroscopy. Such techniques are...

Inbred Strains

These are produced by at least 20 generations of brother x sister mating or its genetic equivalent. For example, parent x offspring mating is one alternative, provided the mating is always to the younger of the two parents (several generations of mating female offspring to the same male is not the same thing, genetically). The effect of this mating scheme is to increase homozygosity within the strain to more than 98 (Figure 9.1), though the approach to complete homozygosity is asymptotic, and...

Present Role Of Laboratory Animals

As discussed previously, rodents, i.e., mice and rats, account for the overwhelming majority of all laboratory animals. This is reflected in the present scientific development of the exponentially growing number of genetically engineered mouse strains produced. Therefore, after outlining the contributions of a wide range of laboratory animals to Physiology and Medicine Nobel Prizes, we discuss the present role of laboratory animals in medical science, with the focus on mice. However, a final...

Human Benefits Of Animal Experimentation

Broadly speaking, modern animal experimentation began in seventeenth-century England and France. It has been central to our understanding of animal and human physiology ever since. A famous early example is William Harvey's investigation of the role of the heart in blood circulation. Observing the hearts of live animals with opened thoraxes, Harvey was able to see that the blood circulates in the body as a result of contractions of the heart. In the first place, then, when the chest of a living...

Institute of Animal Technology IAT

IAT was created in the U.K. to attain proper recognition of the essential contributions to science of those employed to care for laboratory animals. To advance and promote excellence in the technology and practice of laboratory animal care and welfare. In education, IAT makes provision for animal technicians, technologists, and others professionally engaged in the field of animal science to receive appropriate training and qualifications, thus ensuring that they may contribute to advancing...

Ventilation

Animal facilities must have dedicated supply and exhaust air handling units. The supply air must be 100 outside makeup air. The ventilation rate that has proven effective for most animal rooms expressed in terms of fresh air changes per hour cph is around 15 cph. However, this varies between 10 and 20 cph depending on the heat load as well as microbial, particulate, and gaseous contaminants generated in the room, which is dependent on the species and density of animals to be housed in the room....

Contractarianism

Why should we act morally This is a central question in moral philosophy, and one to which the contractarian gives a straightforward answer one should act morally because it is in one's self-interest. The outlook underlying contractarianism is egoism. According to the egoist, when one is obliged to show consideration for other people, this is really for one's own sake. In general, by respecting the rules of morality, one contributes to the maintenance of a society that is essential to one's own...