20 Aug 2019, 10:54 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Genetic quality assurance (QA), including genetic monitoring (GeMo) of inbred strains and background characterization (BC) of genetically altered (GA) animal models, should be an essential component of any QA programme in laboratory animal facilities. Genetic quality control is as important for ensuring the validity of the animal model as health and microbiology monitoring are. It should be required that studies using laboratory rodents, mainly mice and rats, utilize genetically defined animals. This paper, presented by the FELASA Working Group on Genetic Quality Assurance and Genetic Monitoring of Laboratory Murines, describes the objectives of and available methods for genetic QA programmes in rodent facilities. The main goals of any genetic QA programme are: (a) to verify the authenticity and uniformity of inbred stains and substrains, thus ensuring a genetically reliable colony maintenance; (b) to detect possible genetic contamination; and (c) to precisely describe the genetic composition of GA lines. While this publication focuses mainly on mouse and rat genetic QA, the principles will apply to other rodent species some of which are briefly mentioned within the context of inbred and outbred stocks.
20 Aug 2019, 10:54 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
The translational value of osteoarthritis (OA) models is often debated because numerous studies have shown that animal models frequently fail to predict the efficacy of therapies in humans. In part, this failing may be due to the paucity of preclinical studies that include behavioral assessments in their metrics. Behavioral assessments of animal OA models can provide valuable data on the pain and disability associated with disease—sequelae of significant clinical relevance. Clinical definitions of efficacy for OA therapeutics often center on their palliative effects. Thus, the widespread inclusion of behaviors indicative of pain and disability in preclinical animal studies may contribute to greater success identifying clinically relevant interventions. Unfortunately, studies that include behavioral assays still frequently encounter pitfalls in assay selection, protocol consistency, and data/methods transparency. Targeted selection of behavioral assays, with consideration of the array of clinical OA phenotypes and the limitations of individual behavioral assays, is necessary to identify clinically relevant outcomes in OA animal models appropriately. Furthermore, to facilitate accurate comparisons across research groups and studies, it is necessary to improve the transparency of methods. Finally, establishing agreed-upon and clear definitions of behavioral data will reduce the convolution of data both within and between studies. Improvement in these areas is critical to the continued benefit of preclinical animal studies as translationally relevant data in OA research. As such, this review highlights the current state of behavioral analyses in preclinical OA models.
14 Aug 2019, 2:21 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
Animal models for cystic fibrosis (CF) have enhanced our understanding of the pathology and contributed to the development of new treatments. In the field of CF, many animal models have been developed and described. To our knowledge, thus far, none of the reviews of CF animal models has used a systematic methodology. A systematic approach to creating model overviews can lead to an objective, evidence-based choice of an animal model for new research questions. We searched Pubmed and Embase for the currently available animal models for CF. Two independent reviewers screened the results. We included all primary studies describing an animal model for CF. After duplicate removal, 12,304 publications were left. Because of the large number of models, in the current paper, only the genetic models are presented. A total of 636 publications were identified describing genetic animal models for CF in mice, pigs, ferrets, rats and zebrafish. Most of these models have an altered Cftr gene. An overview of basic model characteristics and outcome measures for these genetic models is provided, together with advice on using these data. As far as the authors are aware, this is one of the largest systematic mapping reviews on genetic animal models for CF. It can aid in selecting a suitable model and outcome measures. In general, the reporting quality of the included publications was poor. Further systematic reviews are warranted to determine the quality and translational value of these models further.
11 Aug 2019, 10:02 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with ageing research have developed their own systems to determine intervention points for potential refinements and to identify humane end points. Several good systems are in use, but variations between them could contribute to poor reproducibility of the science achieved. Working with scientific and regulatory communities in the UK, we have reviewed the clinical signs observed in ageing mice and developed recommendations for enhanced monitoring, behaviour assessment, husbandry and veterinary interventions. We advocate that the default time point for enhanced monitoring should be 15 months of age, unless prior information is available. Importantly, the enhanced monitoring should cause no additional harms to the animals. Where a mouse strain is well characterised, the onset of age-related enhanced monitoring may be modified based on knowledge of the onset of an expected age-related clinical sign. In progeroid models where ageing is accelerated, enhanced monitoring may need to be brought forward. Information on the background strain must be considered, as it influences the onset of age-related clinical signs. The range of ageing models currently used means that there will be no ‘one-size fits all’ solution. Increased awareness of the issues will lead to more refined and consistent husbandry of ageing mice, and application of humane end points will help to reduce the numbers of animals maintained for longer than is scientifically justified.
6 Aug 2019, 6:06 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Examining zebrafish populations for the presence of disease is an integral component of managing fish health in research facilities. Currently, many different strategies are used for zebrafish fish health inspections, which is a scenario that may result in subjective and biased diagnostic evaluations. The goal of this study was to compare the success of pathogen detection between a sample size of randomly selected fish (n = 60) that provides 95% confidence in pathogen detection based on a presumed pathogen prevalence level ≥5%, and other subpopulations and sample numbers commonly submitted for diagnostic testing within a 1000 tank, 30,000 fish, recirculating research system. This included fish collected from a sump tank (n = 53), sentinel fish (n = 11), and fish that were found moribund or freshly dead (n = 18). Additionally, five fish from each subpopulation were collected for histopathologic examination. A second study used retrospective data to examine pathogen distribution between systems (n = 2−5) in multi-system facilities (n = 5) using a sample size of 60 fish per system. For the pathogens detected, results supported the use of representative sample numbers rather than smaller numbers of populations considered more at risk. The exception to this is for the moribund/mortality group, which may be a resource for targeted surveillance of select pathogens. Each system within multi-system facilities should be considered separate units in terms of fish health inspections and biosecurity. Development of these evidence-based standards for fish health inspections in zebrafish systems enhances fish welfare, provides identification of potentially zoonotic pathogens, and ensures scientific integrity and reproducibility of research results.
1 Aug 2019, 12:36 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
Chronic pain and subfertility are the main symptoms of concern in women with endometriosis. In order to find new therapeutic options to suppress the pain, translational animal models are indispensable. We have developed a new automated, experimental setup, with full consideration for animal wellbeing, to determine whether operant behaviour can reveal abdominal hyperalgesia in rats with surgically-induced endometriosis, in order to assess whether abdominal hyperalgesia affect behavioural parameters. Endometriosis was induced by transplantation of uterine fragments in the abdominal cavity. Control groups consisted of sham-operated rats and non-operated rats. We have developed an operant chamber (Skinnerbox) which includes a barrier. The rat can climb the barrier in order to reach the food pellet, increasing in this way the pressure to the abdomen. We show that endometriosis rats collect significantly less sugar pellets when compared with the control rats after the introduction of the barrier. In the Skinnerbox experiment, we showed that in a positive operant setting, the introduction of a barrier results in a contrast of operant behaviour of endometriosis rats and control groups, perchance as a result of abdominal discomfort/hyperalgesia due to surgically-induced endometriosis. This is a promising start for the further development of a refined animal model to monitor abdominal discomfort/hyperalgesia in rats with surgically-induced endometriosis.
30 Jul 2019, 6:03 pm
Laboratory Animals
Laboratory Animals, Volume 53, Issue 4, Page 407-407, August 2019.
26 Jul 2019, 1:50 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration. The increased use of anoles in the laboratory has produced a need to establish effective methods of anesthesia, both for routine veterinary procedures and for research procedures. Therefore, we tested the efficacy of different anesthetic treatments in adult female Anolis sagrei. Alfaxalone, dexmedetomidine, hydromorphone, ketamine and tribromoethanol were administered subcutaneously (SC), either alone or combined at varying doses in a total of 64 female anoles. Drug induction time, duration, anesthesia level and adverse effects were assessed. Differences in anesthesia level were observed depending on injection site and drug combination. Alfaxalone/dexmedetomidine and tribromoethanol/dexmedetomidine were the most effective drug combinations for inducing a surgical plane of anesthesia in anoles. Brown anoles injected SC with alfaxalone (30 mg/kg) plus dexmedetomidine (0.1 mg/kg) or with tribromoethanol (400 mg/kg) plus dexmedetomidine (0.1 mg/kg) experienced mean durations of surgical anesthesia levels of 31.2 ± 5.3 and 87.5 ± 19.8 min with full recovery after another 10.9 ± 2.9 and 46.2 ± 41.8 min, respectively. Hydromorphone given with alfaxalone/dexmedetomidine resulted in deep anesthesia with respiratory depression, while ketamine/hydromorphone/dexmedetomidine produced only light to moderate sedation. We determined that alfaxalone/dexmedetomidine or tribromoethanol/dexmedetomidine combinations were sufficient to maintain a lizard under general anesthesia for coeliotomy. This study represents a significant step towards understanding the effects of anesthetic agents in anole lizards and will benefit both veterinary care and research on these animals.
23 Jul 2019, 2:50 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
Nest building behavior has been intensely applied as a parameter for severity assessment in mice. In contrast, only a limited number of studies have reported nest building data from rats. Here, we assessed nest building in rats in two different facilities addressing the hypotheses that the vendor, previous experience with the nesting material as well as sex of the rats has an impact on the performance. Data from two study sites and three raters were compared to obtain information about the robustness of nest complexity scoring. The findings demonstrate a generally poor nest building performance in rats with a pronounced day-to-day fluctuation, and site-specific differences. Application of a newly developed scoring system resulted in an intermediate inter-rater reliability. Previous experience with the nesting material did not exert a consistent impact on nest complexity scores. Sex differences proved to depend on vendor and animal facility without consistent findings supporting a superior performance in female or male rats. In conclusion, our findings argue against a robust and consistent influence of sex and familiarity with the nesting material. The comparison between facilities suggests that local conditions need to be considered as influencing factors, which should be explored in more detail by future multicenter approaches. Considering the day-to-day fluctuation and the intermediate inter-rater reliability, we highly recommend to base nest complexity evaluation on means from several subsequent days analyzed by a group of experienced raters.
27 Jun 2019, 10:01 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Since it was introduced 20 years ago, tamoxifen-inducible genetic recombination in vivo has become a standard tool in many fields. This technique has great utility, allowing precise temporal and spatial gene recombination mediated by expression of a Cre recombinase-oestrogen receptor hormone binding domain fusion protein. It is frequently used in developmental biology, either for accurate spatio-temporal gene deletion or for lineage-labelling. Administration of high doses of tamoxifen can rapidly induce abortion in pregnant mice but this can be partially overcome by progesterone co-administration. However, administration of tamoxifen to pregnant mice early in pregnancy may have potentially lethal effects on the mother independently of abortion, and can also severely perturb embryonic development. Despite this, only a few published studies mention this fact in passing, and standard parameters for successful or unsuccessful use of tamoxifen in pregnant mice have not been reported. Therefore, in the interests of providing a framework for more humane animal research, we describe our experiences of tamoxifen administration during early gestation in mice. These observations should assist the design of future studies in accordance with the principles of the three Rs (Replacement, Reduction and Refinement of Animals in Research).