Ilar Journal最新文献

Biomedical research involving animal models continues to provide important insights into disease pathogenesis and treatment of diseases that impact human health. In particular, nonhuman primates (NHPs) have been used extensively in translational research due to their phylogenetic proximity to humans and similarities to disease pathogenesis and treatment responses as assessed in clinical trials. Microscopic changes in tissues remain a significant endpoint in studies involving these models. Spontaneous, expected (ie, incidental or background) histopathologic changes are commonly encountered and influenced by species, genetic variations, age, and geographical origin of animals, including exposure to infectious or parasitic agents. Often, the background findings confound study-related changes, because numbers of NHPs used in research are limited by animal welfare and other considerations. Moreover, background findings in NHPs can be exacerbated by experimental conditions such as treatment with xenobiotics (eg, infectious morphological changes related to immunosuppressive therapy). This review and summary of research-relevant conditions and pathology in rhesus and cynomolgus macaques, baboons, African green monkeys, common marmosets, tamarins, and squirrel and owl monkeys aims to improve the interpretation and validity of NHP studies.

We provide here a current overview of marmoset (Callithrix) evolution, hybridization, species biology, basic/biomedical research, and conservation initiatives. Composed of 2 subgroups, the aurita group (C aurita and C flaviceps) and the jacchus group (C geoffroyi, C jacchus, C kuhlii, and C penicillata), this relatively young primate radiation is endemic to the Brazilian Cerrado, Caatinga, and Atlantic Forest biomes. Significant impacts on Callithrix within these biomes resulting from anthropogenic activity include (1) population declines, particularly for the aurita group; (2) widespread geographic displacement, biological invasions, and range expansions of C jacchus and C penicillata; (3) anthropogenic hybridization; and (4) epizootic Yellow Fever and Zika viral outbreaks. A number of Brazilian legal and conservation initiatives are now in place to protect the threatened aurita group and increase research about them. Due to their small size and rapid life history, marmosets are prized biomedical models. As a result, there are increasingly sophisticated genomic Callithrix resources available and burgeoning marmoset functional, immuno-, and epigenomic research. In both the laboratory and the wild, marmosets have given us insight into cognition, social group dynamics, human disease, and pregnancy. Callithrix jacchus and C penicillata are emerging neotropical primate models for arbovirus disease, including Dengue and Zika. Wild marmoset populations are helping us understand sylvatic transmission and human spillover of Zika and Yellow Fever viruses. All of these factors are positioning marmosets as preeminent models to facilitate understanding of facets of evolution, hybridization, conservation, human disease, and emerging infectious diseases.

Interest in marmosets as research models has seen exponential growth over the last decade, especially given that the research community is eager to improve on gaps with historical animal models for behavioral and cognitive disorders. The spectrum of human disease traits that present naturally in marmosets, as well as the range of analogous human behaviors that can be assessed in marmosets, makes them ideally suited as translational models for behavioral and cognitive disorders. Regardless of the specific research aims of any project, without close collaboration between researchers, veterinarians, and animal care staff, it would be impossible to meet these goals. Behavior is inherently variable, as are marmosets that are genetically and phenotypically diverse. Thus, to ensure rigor, reliability, and reproducibility in results, it is important that in the research environment, the animal's daily husbandry and veterinary needs are being met and align with the research goals while keeping the welfare of the animal the most critical and highest priority. Much of the information described herein provides details on key components for successful behavioral testing, based on a compendium of methods from peer-reviewed publications and our own experiences. Specific areas highlighted include habituation procedures, selection of appropriate rewards, optimization of testing environments, and ways to integrate regular veterinary and husbandry procedures into the research program with minimal disruptions to the behavioral testing plan. This article aims to provide a broad foundation for researchers new to establishing behavioral and cognitive testing paradigms in marmosets and especially for the veterinary and husbandry colleagues who are indispensable collaborators of these research projects.

The publication of reproducible, replicable, and translatable data in studies utilizing animal models is a scientific, practical, and ethical necessity. This requires careful planning and execution of experiments and accurate reporting of results. Recognition that numerous developmental, environmental, and test-related factors can affect experimental outcomes is essential for a quality study design. Factors commonly considered when designing studies utilizing aquatic animal species include strain, sex, or age of the animal; water quality; temperature; and acoustic and light conditions. However, in the aquatic environment, it is equally important to consider normal species behavior, group dynamics, stocking density, and environmental complexity, including tank design and structural enrichment. Here, we will outline normal species and social behavior of 2 commonly used aquatic species: zebrafish (Danio rerio) and Xenopus (X. laevis and X. tropicalis). We also provide examples as to how these behaviors and the complexity of the tank environment can influence research results and provide general recommendations to assist with improvement of reproducibility and replicability, particularly as it pertains to behavior and environmental complexity, when utilizing these popular aquatic models.

Environmental complexity is an experimental paradigm as well as a potential part of animals' everyday housing experiences. In experimental uses, researchers add complexity to stimulate brain development, delay degenerative brain changes, elicit more naturalistic behaviors, and test learning and memory. Complexity can exacerbate or mitigate behavioral problems, give animals a sense of control, and allow for expression of highly driven, species-typical behaviors that can improve animal welfare. Complex environments should be designed thoughtfully with the animal's natural behaviors in mind, reported faithfully in the literature, and evaluated carefully for unexpected effects.

For more than 50 years, the research community has made strides to better determine the nutrient requirements for many common laboratory animal species. This work has resulted in high-quality animal feeds that can optimize growth, maintenance, and reproduction in most species. We have a much better understanding of the role that individual nutrients play in physiological responses. Today, diet is often considered as an independent variable in experimental design, and specialized diet formulations for experimental purposes are widely used. In contrast, drinking water provided to laboratory animals has rarely been a consideration in experimental design except in studies of specific water-borne microbial or chemical contaminants. As we advance in the precision of scientific measurements, we are constantly discovering previously unrecognized sources of experimental variability. This is the nature of science. However, science is suffering from a lack of experimental reproducibility or replicability that undermines public trust. The issue of reproducibility/replicability is especially sensitive when laboratory animals are involved since we have the ethical responsibility to assure that laboratory animals are used wisely. One way to reduce problems with reproducibility/replicability is to have a strong understanding of potential sources of inherent variability in the system under study and to provide "…a clear, specific, and complete description of how the reported results were reached [1]." A primary intent of this review is to provide the reader with a high-level overview of some basic elements of laboratory animal nutrition, methods used in the manufacturing of feeds, sources of drinking water, and general methods of water purification. The goal is to provide background on contemporary issues regarding how diet and drinking water might serve as a source of extrinsic variability that can impact animal health, study design, and experimental outcomes and provide suggestions on how to mitigate these effects.

Review of the use of nonexperimental xenobiotics in terrestrial animal models and the potential unintended consequences of these compounds, including drug-related side effects and adverse reactions.

As mentioned in other chapters, reproducibility of research data is very complicated and has numerous contributors for concerns. This chapter will discuss the animal housing systems and corresponding husbandry practices in regard to current practices and known and potential confounders in the research environment. This area has a very high impact for reproducibility and comparability of study data outcomes.