Journal: Lab animal
Domesticated porcine species are commonly used in studies of wound healing, owing to similarities between porcine skin and human skin. Such studies often involve wound dressings, and keeping these dressings intact on the animal can be a challenge. The authors describe a novel and simple technique for constructing a fitted neoprene garment for pigs that covers dressings and maintains their integrity during experiments.
Evaluating the behavior of mice and rats has substantially contributed to the progress of research in many scientific fields. Researchers commonly observe recorded video of animal behavior and manually record their observations for later analysis, but this approach has several limitations. The authors developed an automated system for tracking and analyzing the behavior of rodents that is based on radio frequency identification (RFID) in an ultra-high-frequency bandwidth. They provide an overview of the system’s hardware and software components as well as describe their technique for surgically implanting passive RFID tags in mice. Finally, the authors present the findings of two validation studies to compare the accuracy of the RFID system versus commonly used approaches for evaluating the locomotor activity and object exploration of mice.
Handling a rodent disease outbreak in a facility can be a challenge. After the University of Colorado Denver Office of Laboratory Animal Resources enhanced its sentinel monitoring program, > 90% of the animal colonies housed in a vivarium at the Anschutz Medical Campus (with an area of 50,000 net ft(2)), serving the labs of > 250 principal investigators, tested positive for multiple infective agents including mouse parvovirus, fur mites, pinworms and epizootic diarrhea of infant mice. The authors detail the process by which they planned and executed a shutdown and a decontamination of the facility, which involved the rederivation or cryopreservation of > 400 unique genetically modified mouse lines. The authors discuss the aspects of the project that were successful as well as those that could have been improved.
Repeated, low-dose administration of streptozotocin (STZ) is widely used to induce insulin-dependent diabetes mellitus in mice. The authors adapted this method using neonatal mice and determined the long-term effects of STZ injection in the mice. After receiving intraperitoneal injections of STZ at postnatal day 3 (P3), P4 and P8, male and female mice were hyperglycemic by week 4. A clear sex difference was found, with blood glucose levels in STZ-treated males remaining higher than those in STZ-treated females until week 23. Whereas STZ-treated males remained hyperglycemic until week 23, STZ-treated females did not have significantly higher glucose levels than control mice after week 18. Additionally, STZ-treated mice had neoplastic lesions in their livers by week 4, with a progression in the severity of these lesions until week 24. The results confirm that, in addition to pancreatic beta cell toxicity, STZ has an oncogenic effect on the liver when administered to neonates.
Embryo transfer is a surgical technique that is widely used in reproductive biotechnology. Despite the ethical obligation to relieve animals' post-operative pain, analgesia is not routinely provided after embryo transfer surgery because it has been suggested that analgesics may be detrimental to embryo survival. Studies suggest, however, that the potential for adverse effects varies depending on the type of analgesic used and the timing of its administration. The authors carried out a study to determine whether pre-operatively administered tramadol, a synthetic analogue of codeine, influenced birth rate, litter survival or the post-operative body weights of surrogate dams. Compared with controls that were not given any analgesic, surrogate dams given tramadol had similar birth rates and similar body weights at all time points. The tramadol-treated surrogate dams showed a statistically significant increase in the number of offspring that survived to weaning. The authors conclude that pre-operatively administered tramadol does not harm the success rate of embryo transfer surgery and even may improve litter survival.
Rabbits are commonly used in biomedical research and might undergo potentially painful procedures during the course of a study. This column discusses the rabbit facial grimace scale as a tool for monitoring post-procedural pain and explains how it can be incorporated into a worksheet for evaluating rabbit wellness.
This focus issue of Lab Animal coincides with a tipping point in biomedical research. For the first time, the scale of the reproducibility and translatability crisis is widely understood beyond the small cadre of researchers who have been studying it and the pharmaceutical and biotech companies who have been living it. Here we argue that an emerging literature, including the papers in this focus issue, has begun to congeal around a set of recurring themes, which themselves represent a paradigm shift. This paradigm shift can be characterized at the micro level as a shift from asking “what have we controlled for in this model?” to asking “what have we chosen to ignore in this model, and at what cost?” At the macro level, it is a shift from viewing animals as tools (the furry test tube), to viewing them as patients in an equivalent human medical study. We feel that we are witnessing the birth of a new discipline, which we term Therioepistemology, or the study of how knowledge is gained from animal research. In this paper, we outline six questions that serve as a heuristic for critically evaluating animal-based biomedical research from a therioepistemological perspective. These six questions sketch out the broad reaches of this new discipline, though they may change or be added to as this field evolves. Ultimately, by formalizing therioepistemology as a discipline, we can begin to discuss best practices that will improve the reproducibility and translatability of animal-based research, with concomitant benefits in terms of human health and animal well-being.
Model organism databases (MODs) have been collecting and integrating biomedical research data for 30 years and were designed to meet specific needs of each model organism research community. The contributions of model organism research to understanding biological systems would be hard to overstate. Modern molecular biology methods and cost reductions in nucleotide sequencing have opened avenues for direct application of model organism research to elucidating mechanisms of human diseases. Thus, the mandate for model organism research and databases has now grown to include facilitating use of these data in translational applications. Challenges in meeting this opportunity include the distribution of research data across many databases and websites, a lack of data format standards for some data types, and sustainability of scale and cost for genomic database resources like MODs. The issues of widely distributed data and application of data standards are some of the challenges addressed by FAIR (Findable, Accessible, Interoperable, and Re-usable) data principles. The Alliance of Genome Resources is now moving to address these challenges by bringing together expertly curated research data from fly, mouse, rat, worm, yeast, zebrafish, and the Gene Ontology consortium. Centralized multi-species data access, integration, and format standardization will lower the data utilization barrier in comparative genomics and translational applications and will provide a framework in which sustainable scale and cost can be addressed. This article presents a brief historical perspective on how the Alliance model organisms are complementary and how they have already contributed to understanding the etiology of human diseases. In addition, we discuss four challenges for using data from MODs in translational applications and how the Alliance is working to address them, in part by applying FAIR data principles. Ultimately, combined data from these animal models are more powerful than the sum of the parts.
Mounting evidence suggests that environmental stress experienced in utero (for example, maternal nutritional deficits) establishes a predisposition in the newborn to the development of chronic diseases later in life. This concept is often referred to as the “fetal origins hypothesis” or “developmental origins of health and disease”. Since its first proposal, epigenetics has emerged as an underlying mechanism explaining how environmental cues become gestationally “encoded”. Many of the enzymes that impart and maintain epigenetic modifications are highly sensitive to nutrient availability, which can be influenced by the metabolic activities of the intestinal microbiota. Therefore, the maternal microbiome has the potential to influence epigenetics in utero and modulate offspring’s long-term health trajectories. Here we summarize the current understanding of the interactions that occur between the maternal gut microbiome and the essential nutrient choline, that is not only required for fetal development and epigenetic regulation but is also a growth substrate for some microbes. Bacteria able to metabolize choline benefit from the presence of this nutrient and compete with the host for its access, which under extreme conditions may elicit signatures of choline deficiency. Another consequence of bacterial choline metabolism is the accumulation of the pro-inflammatory, pro-thrombotic metabolite trimethylamine-N-oxide (TMAO). Finally, we discuss how these different facets of microbial choline metabolism may influence infant development and health trajectories via epigenetic mechanisms and more broadly place a call to action to better understand how maternal microbial metabolism can shape their offspring’s propensity to chronic disease development later in life.