Journal of the American Association for Laboratory Animal Science : JAALAS最新文献

A standard 2-wk cage change frequency for individually ventilated mouse cages is used in many research facilities, with negligible effects on animal health and welfare. However, these techniques rely on subjective visual evaluations and often require spot changes. In this study, we describe the use and validation of digital monitoring technology to objectively determine the necessity of a cage change for mice. We used a machine learning/artificial intelligence algorithm that was trained by annotating human observations of soiled bedding to correlate with the Bedding Status Index (BSI), a digital measure quantifying bedding 'wetness.' Training of the algorithm was performed using various mouse strains of different age, sex, and cage densities to account for variability of these factors. Through constant user feedback and increased datasets, we were able to identify soiled cages with an accuracy >90% for cages with higher densities (for example, 5 animals per cage), while lower densities exhibited slightly reduced accuracy levels (the lowest accuracy was attributed to single-housed mice, at 76%). Our data show that the average change intervals for most average-sized mice ranged between 3 and 6 wk depending on the number of animals in the cage, which is significantly different from the standard 2-wk change used in our facility. Retired breeders and larger mice tended to have a shorter cage change interval as determined by the algorithm. These results show that the Bedding Status Index, which measures an intracage environmental variable, namely bedding wetness, can be used as a marker for cage change. The extended cage change schedule did not affect intracage ammonia, CO2 levels, mouse growth rates, or circadian rhythm metrics. Using digital alerts to determine the need for a cage change resulted in a 65% to 70% reduction in the number of cage changes needed, indicating that this method can improve operational efficiency by reducing cage changes, cage wash time, staff labor, and resource consumption.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are the major prevalent liver diseases and growing public health problems worldwide. Because MASLD/MASH is known as a risk for progression to cirrhosis and development of hepatocellular carcinoma, therapeutic approaches and biomarkers that reflect the presence and progression of the disease are needed. In recent years, the usefulness of serum L-FABP levels has been reported for monitoring of hepatocellular damage in various liver diseases including MASLD/MASH in humans. Furthermore, it is reported that hepatic L-FABP is a potential therapeutic target. The purpose of this study was to validate the usefulness of serum L-FABP as a liver damage biomarker in the mouse model of MASLD/MASH and to evaluate the function of L-FABP in the pathogenesis of MASLD/MASH. First, we evaluated the changes in serum L-FABP as a liver damage biomarker using a mouse model of MASLD/MASH fed a choline-deficient, methionine-lowered, amino acid-defined, high-fat diet. The results demonstrated that serum L-FABP levels in the MASLD/MASH model continuously increased with the progression of steatosis and correlated with histopathologic changes. Serum L-FABP may be a useful biomarker for liver disease with respect to translational research bridging between animal models and human clinical research. Further, we showed that in human L-FABP chromosomal transgenic mice L-FABP had a suppressive effect on the gene expression associated with oxidative stress, fibrosis, and inflammation in the MASLD/MASH model. L-FABP is not only a biomarker in the blood but also has the functional aspect of hepatoprotection against MASLD/MASH.

Fenbendazole (FBZ) treatment for pinworm infections is generally safe and effective but not without concern for potential research complications in its application to laboratory animal colonies. Previously, dietary FBZ was found to impair motor performance in C57BL/6N mice, an effect that endured at least 2 wk posttreatment. These findings raised the possibility that FBZ treatment would complicate our own research on poststroke motor function in C57BL/6J mice. Here we present the results of a study that tested this possibility in the context of facility-wide FBZ treatment based on repeated measures in a skilled reaching task that is extremely sensitive to forelimb motor impairments. Mice of both sexes that were proficient in the reaching task were measured in their performance of the task in each of the 4 wk preceding, 7 wk during, and 2 wk after dietary FBZ treatment that alternated weekly between therapeutic and subtherapeutic doses. There was no indication of a notable decrement or other change in reaching performance during or after FBZ treatment (mean ± SE percent success before, during, and after treatment = 57 ± 2, 53 ± 2, and 60 ± 2; n = 20). Performance stability in FBZ-treated mice was similar to that of untreated mice. These results are significant for revealing a lack of noticeable influence of FBZ on a commonly used measure of motor function in a widely used mouse strain. The difference in FBZ effects relative to the prior study could reflect substrain-dependency (6N compared with 6J) and/or differences in motor behavioral measures.

Research involving animals is pivotal to advancing biomedical and veterinary sciences, contributing to discoveries that have saved countless lives and improved global health. However, the field faces increasing scrutiny from ethical, scientific, and societal perspectives. This paper applies a strategic Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis, adapted from traditional business planning, to critically evaluate the current landscape of animal research, offering a balanced perspective on its contributions and challenges. While typically used to assess organizational performance, here the framework is reinterpreted to provide a structured, holistic view of the internal and external factors shaping ethical, scientific, and societal aspects of animal research. Strengths include its foundational role in Nobel Prize-winning discoveries, medical advancements, and therapeutic safety. Key weaknesses, such as public mistrust, ethical concerns, resource limitations, and rigor and reproducibility, are examined. Opportunities lie in the advancement of study refinements, improved methodologies, and fostering stakeholder communication. Threats such as misunderstanding, regulatory complexities, and resource constraints are addressed through strategic recommendations, including investment in Replacement, Reduction, and Refinement (3Rs), effective public engagement, and global harmonization of standards. This paper concludes by presenting an actionable roadmap to ensure the continued ethical and impactful use of animals in research while embracing innovation and maintaining public trust.

Nuances related to the milieu of the gastrointestinal tract have led to investigations of environmental (or extrinsic) factors, like feed sources and fluid intake, and their influences on the gut microbiome in research animals. Water is typically provided to laboratory mice either by reusable water bottle (RWB), housing rack automatic water (RAW) delivery, or single-use disposable plastic pouch (DPP). In this study, the influence of differing water delivery methods on gut microbiome stability was evaluated in immunocompetent (n = 36 B6; 18 male [M]:18 female [F]) and immunocompromised (n = 36 NOG; 18 M:18 F) strains of mice. Mice were housed on a single IVC rack in sex-specific groups and provided with autoclaved caging and bedding, irradiated feed, and chlorinated, reverse-osmosis water provided by one of 3 delivery methods (8 cages per method). Access to the room was restricted to select personnel to conduct animal care and sample collection tasks. Fecal pellets (n = 2) were collected from each animal every other week, and water samples were collected weekly for analysis. Over the course of the study, bacteria were detected in 11% of the RWB samples (7 of 63) and 4% of the RAW samples (1 of 25). DPP samples were consistently free of bacterial contamination. Shotgun metagenomics and statistical analyses revealed overt shifts in gut microbiota in the majority of mice throughout the study (21 of 25 cages). Histologic examinations of organs from representative clinically normal study mice (n = 12) were unremarkable. With minimal exceptions, microbiome shifts were statistically significant across cage cohorts, despite attempts to control experimental variables. This study is the first to demonstrate that the water delivery method does not impart a significant influence on gut microbiota stability in research rodents and highlights the need to document water type, treatment, and delivery method as extrinsic factors in reporting animal studies.

Stereotaxic surgery is a common procedure in neuroscience, yet effective analgesic protocols require further study and refinement to optimize the analgesia used in invasive procedures and to improve animal welfare. This study evaluated the effects of tramadol and meloxicam, alone or combined, on pain management following craniotomy in rats. Forty Wistar-Han rats were divided into 5 groups: saline + anesthesia (SAL+ANE), saline + surgery (SAL+SUR), tramadol + surgery (TRA+SUR), meloxicam + surgery (MEL+SUR), and tramadol/meloxicam + surgery (TRA/MEL+SUR). Treatments (saline, 0.2 mL; tramadol, 17.8 mg/kg; meloxicam, 1.5 mg/kg) were administered subcutaneously every 12 h for 72 h. The animals underwent anesthesia or surgery 30 min after the first injection. Postoperative assessments included open field testing, a grooming transfer test, nesting behavior, body weight, and food/water intake. Surgery induced behavioral changes occured within 48 h. SAL+SUR and MEL+SUR groups showed increased locomotion and rearing, while SAL+SUR, TRA+SUR, and TRA/MEL+SUR groups had reduced grooming. TRA/MEL+SUR and SAL+SUR groups had the lowest grooming transfer test scores, and TRA/MEL+SUR rats displayed reduced nesting behavior. Craniotomy caused mild pain lasting at least 48 h. Although no optimal analgesic was identified, providing analgesia and refining surgical techniques are essential to ensure animal welfare.

We studied the effect of different filler items on rhesus macaques' use of a feeding enrichment device called the 'browsing bowl.' We examined use of the device as affected by calories, sugar content, and volume of different fillers as well as the presentation of each filler as 1) whole, loose, or smeared and 2) frozen or not frozen. In addition, we examined the impact of age and sex of the monkeys on use of the device. Fifty-eight macaques were observed across 30-min sessions with the device, with one session for each of 12 different fillers. Scans occurred every 2.5 min, at which point the monkeys were scored as interacting or not interacting with the device. Subjects were recorded as interacting with the device during 47.6% of all observed scans and during 80% of the first 2 scans per session. Frozen items were associated with a significantly higher mean engagement (ME; proportion of observed scans in which animals engaged with the device) than items that were not frozen items (t(57) = 12.91, P < 0.001). Whole presentations were associated with a significantly higher ME than for smeared (P < 0.001) or loose (P = 0.005) items. Loose items were associated with a significantly higher ME (P < 0.001) than for smeared items. Sugar and calorie content did not impact use of the device. Younger monkeys used the device more than for older monkeys, and female monkeys used the device more than did males. We conclude that some filler items encourage more foraging behavior than others, and that it is possible to generate relatively long (up to 30 min) foraging bouts by altering the presentation of foods rather than increasing calories or sugar content. Indeed, some fillers were still present and engaged with at the end of the observation session.

Thymomas are tumors originating from thymic epithelial cells and are uncommon in animals, including pets and domestic and laboratory animals. A 10-wk-old female ICR (CD-1) mouse in the control group of a toxicity study presented a thymic mass consisting of epithelial and lymphocytic components. Histopathological evaluation showed epithelioid neoplastic cells intermixed with small lymphocytes and areas of hemorrhage. Immunohistochemistry revealed positivity for proliferating cell nuclear antigen and pan-cytokeratin (AE1/AE3), and negativity for S100 and vimentin. Based on these features, the mass was diagnosed as a benign thymoma. To the best of our knowledge, this is the first report of a thymoma in a laboratory mouse at such a young age.

The Veterinary Consortium for Research Animal Care and Welfare (VCRACW or Consortium) was established in 2019 to provide accurate information to the public, lawmakers, and the scientific community about the veterinary care and welfare of research animals. The consortium includes 2 representatives from 4 member organizations: AALAS, American College of Laboratory Animal Medicine (ACLAM), Association of Primate Veterinarians (APV), and American Society of Laboratory Animal Practitioners (ASLAP). As time for revision of the Guide for the Care and Use of Laboratory Animals (Guide) approaches, the Consortium sought to conduct a survey of the animal research community with the goal of generating objective data and providing analysis that would identify priorities for updating the Guide. An initial survey was conducted of stakeholders from the 4 member organizations. "Chapter 3 Environment, Housing, and Management" was identified as most in need of revision. The "Terrestrial Housing" section was ranked most in need of revision, followed by the "Terrestrial Environment" and "Terrestrial Management" sections, all from Chapter 3. Of the top ten topics the respondents identified that needed revision, 9 were from Chapter 3. Open-ended questions asked respondents to describe key issues that needed to be revised and what new topics should be added, including references. Most responses (199) related to the revision of Chapter 3 and focused on space requirements and environment. New topics proposed for inclusion ranged from additional information on ferrets, agricultural species, and cephalopods to new sections on mental health for employees and study design and additional information pertaining to operations. As a follow-up to the original survey, 5 additional questions were posed to ACLAM diplomates and National Association for Biomedical Research (NABR) members. These questions focused on topics that came from responses to and discussion about the original survey. These topics included the use of must, should, and may; inclusion of additional species; inclusion of mental health topics; future format; and funding source for the Guide. The results of both surveys are presented here. The Consortium believes that these data could be used to refine and revise portions of the Guide to ensure it remains the most current and relevant reference document for the care and use of research animals.

The use of animals in teaching and research dates back over 2,000 y BCE. However, animal protection laws and regulatory agencies only emerged in the 19th century CE. This study provides a qualitative comparative analysis of legislation related to the use of animals in teaching and research activities across 35 American countries. The research evaluated key aspects, including the direct or indirect constitutional recognition of animal protection, the presence of specific or general laws, the establishment and regulation of animal care and use committees, adherence to the 3Rs (Replacement, Reduction, and Refinement) principle, and requirements for facilities, animal care, and personnel. The results revealed significant heterogeneity in regulatory frameworks, with only a few countries having specific laws (8 out of 35), while most rely on general animal protection laws (32 out of 35), with or without specific provisions on the subject. Animal care and use committees, despite their importance, are not universally mandatory, and their regulatory structures vary widely, with legislation explicitly regulating them found in only 9 of the 35 countries analyzed. The 3Rs principle is present in most countries, with "refinement" being the most commonly observed, followed by "replacement" and "reduction." In addition, legal provisions regarding requirements for facilities, housing and care of animals, and personnel responsible for their use and welfare were largely absent in the legislation analyzed, often supplemented by nonmandatory international guidelines. This study highlights the need for standardized regulations that can help achieve animal welfare, maintain ethical practices, and promote greater consistency in oversight mechanisms across the Americas.