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

In this study we investigated the sedative, anesthetic, and pulmonary histopathologic effects of dexmedetomidine/morphine (DM) and xylazine/morphine (XM) in sheep. We hypothesized that DM would provide profound sedation and better maintain physiologic parameters under anesthesia than XM in sheep undergoing laparoscopic surgery. Nineteen male sheep were premedicated with either DM (dexmedetomidine [0.006 mg/kg] and morphine [0.3 mg/kg]) or XM (xylazine [0.1 mg/kg] and morphine [0.3 mg/kg]). After DM or XM administration, 3 blinded veterinarians evaluated sedation scores (0 [no sedation], 1 [mild], 2 [moderate], 3 [severe]). Sheep were induced with intravenous tiletamine/zolazepam, intubated, and maintained with isoflurane in 100% oxygen. Anesthetic parameters were monitored for 60 min, including heart rate, respiratory rate, indirect blood pressure, oxygen saturation, end-tidal carbon dioxide, body temperature, arterial blood gas analysis, and isoflurane requirement. At the end of the procedure, the sheep were euthanized, and lung pathology (pulmonary edema) was assessed. The results showed that the sedation scores did not differ between DM (0.8 [0.4 to 1.0]) and XM (1.0 [1.0 to 1.0]). In addition, the anesthetic parameters were comparable between the groups, but the DM group exhibited a higher heart rate than the XM group. Finally, marked pulmonary changes, consistent with pulmonary edema, were observed in the XM group. In conclusion, DM and XM provided similar sedation and physiologic stability under isoflurane anesthesia, but DM may help minimize bradycardia and was associated with less evidence of pulmonary edema.

Extended-release buprenorphine formulations are commonly used to control postoperative pain in rodents with minimal handling-related stress. An FDA-indexed formulation is now available that has been demonstrated safe and effective with ketamine-xylazine and isoflurane anesthesia; however, safe use in combination with tribromoethanol, a nonpharmaceutical-grade anesthetic sometimes favored for short, high-volume procedures, has not been reported. Effects on pregnancy and offspring have also not been examined. In this study we compared the safety and efficacy of the FDA-indexed formulation at the labeled dose (3.25 mg/kg) to the compounded extended-release buprenorphine formulation used by the centralized Transgenic Core at our institution at the manufacturer-recommended dosage (1 mg/kg) in CD-1 mice under tribromoethanol anesthesia. A pilot (n = 5 females per drug) was initially conducted with anesthetic and analgesic in the absence of surgical manipulation, after which the formulations were compared in embryo transfer and vasectomy surgeries (n = 10 males or females per drug). Relative efficacy was assessed at 6, 24, 48, and 72 h after surgery using a cageside ethogram, frequency of rearing behavior compared with baseline, and weight change. No differences were seen between analgesic treatment groups. Safety was evaluated by intraoperative respiratory rate, recovery time, incidence of analgesic injection site lesions, and gross necropsy. Ulceration was only observed at the injection site of mice receiving compounded drug; no other differences between treatments were observed. Effects on pregnancy were evaluated by comparing pregnancy success, litter size, and pup weight at weaning between treatment groups in the initial experiment and embryo transfers subsequently performed by the Transgenic Core (n = 19 sets). No significant differences were identified. These results indicate that both formulations can be safely used in vasectomy and embryo transfer surgeries under tribromoethanol anesthesia; however, the FDA-indexed product may improve welfare by decreasing injection site ulceration compared with the compounded formulation.

Storage mites are environmental pests that commonly invade hay, grain, or stored food. While generally regarded as harmless, they have been reported to elicit allergic reactions in both humans and animals. Although storage mites are considered environmental contaminants, this case report describes an infestation of storage mites on rats (Rattus norvegicus) in a laboratory animal facility. Despite traditional diagnostic methods initially revealing negative results, mites were consistently observed under repeated direct microscopic examinations of the animals. Eventual positive pelage tapes confirmed the presence of the ectoparasites and identified them as mold or cheese mites (Tyrophagus brevicrinatus or Tyrophagus putrescentiae) via Sanger sequencing. To our knowledge, this report is the first to implement permethrin-soaked cotton balls for the successful treatment of mold mites in an entire rat colony. Furthermore, considering the initial negative diagnostic results, this report emphasizes the pelage tape method as highly susceptible to false negatives.

Improved animal models of endometriosis are needed to accurately represent the pathophysiology of human disease and identify new therapeutic targets that do not compromise fertility. There is tremendous heterogeneity among published rodent models of endometriosis, and the etiology and pathogenesis of endometriosis remain undetermined. The vast majority of endometriosis is found in menstruating women; however, no published mouse models have induced endometriosis in a menstruating mouse, further limiting our understanding of the disease. Our goal was to develop a novel, translationally relevant mouse model of endometriosis in a menstruating mouse by transplanting donor menstrual endometrium into the peritoneal cavity of menstruating, immunocompetent, intact recipients. We initially compared 4 different experimental groups to optimize implanted menstrual tissue type and method of implantation into intact, normally cycling recipient mice. To further optimize this model, a novel fifth experimental group was compared in which discrete pieces of menstrual donor endometrium were implanted via laparoscopy into menstruating recipient mice. Lesions were confirmed to be endometriosis based on histopathology. The use of laparoscopy to place discrete fragments of menstrual phase endometrium intraabdominally was the most effective method for induction of endometriosis. This method was just as effective when used to induce endometriosis in menstruating recipient mice. Menstruating mice returned to normal estrus cyclicity after induction of disease, which can allow for assessment of therapeutic interventions on fertility. This is a novel translationally relevant mouse model of endometriosis in a menstruating mouse that can be used to explore and elucidate the etiology and pathogenesis of this disease.

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.