Phase response curve to melatonin in a putatively diurnal rodent, Octodon degus

The degu (Octodon degus) is a diurnal rodent, although phase inversions to nocturnal behavior have been reported under specific laboratory conditions. The reliability of this animal as a diurnal model of sleep therefore requires further characterization of intrinsic circadian pacemaker properties. A phase response curve to light has been reported in the degu, and is consistent with other diurnal animals. This study reports a phase response curve to melatonin in the degu, which is distinct in orientation from the light curve.     

Phase Response Curve to Melatonin in a Putatively Diurnal Rodent,Octodon degus

The degu (Octodon degus) is a diurnal rodent, although phase inversions to nocturnal behavior have been reported under specific laboratory conditions. The reliability of this animal as a diurnal model of sleep therefore requires further characterization of intrinsic circadian pacemaker properties. A phase response curve to light has been reported in the degu, and is consistent with other diurnal animals. This study reports a phase response curve to melatonin in the degu, which is distinct in orientation from the light curve.     

Environmental enrichment for laboratory rodents

Modernization of housing and husbandry techniques for rodents has minimized confounding variables. The result has been vastly improved health maintenance and reproducibility of research findings, advances that have decreased the numbers of animals needed to attain statistically significant results. Even though not all aspects of rodent manipulation have been strictly defined, as housing and handling procedures have become increasingly standardized, many animal care personnel have recognized the lack of complexity of the rodents' environment. Concern for this aspect of animal well-being has led many research facilities to provide "environmental enrichment" for rodents. Additionally, regulatory agencies in the United States and Europe have also been increasingly concerned about this issue relative to laboratory animal husbandry. However, little is known about the influence such husbandry modifications may have on biological parameters. In this article, laws and guidelines relating to rodent enrichment are reviewed, the natural behaviors of select rodent species are discussed, and an overview of widely used types of enrichment in laboratory rodent management is provided. The literature evaluating effects of rodent enrichment is reviewed both in terms of neurological development and as an experimental variable, and results of a study evaluating the effect of enrichment on immune and physiological parameters are reported. Survey data on current enrichment practices in a large multi-institutional organization are presented, and practical aspects requiring consideration when devising a rodent enrichment program are discussed.     

啮齿动物活动模式的几种数值指标

提出评估啮齿动物活动模式的4 种定量指标: θ、λ、Φ和η。θ主要衡量动物日活动强度的差异程度; λ用于判断动物活动究竟是以昼行性为主还是以夜行性为主; Φ用来甄别动物的活动究竟接近于(或者属于) 单峰型还是接近于(或属于) 双峰型; 而η则是度量动物绝对活动强度的指标。这4 种数值指标分别从不同角度阐明动物活动模式的特征, 可为分析比较动物的活动模式提供参考依据。     

Laboratory animal science issues in the design and conduct of studies with endocrine-active compounds

The use of rodent models for research and testing on endocrine-active compounds necessitates an awareness of a number of laboratory animal science issues to standardize bioassay methods and facilitate reproducibility of results between laboratories. These issues are not unique to endocrine research but are particularly important in this field due to the complexities and interdependencies of the endocrine system, coupled with the inherently sensitive and variable nature of physiological endpoints. Standardization of animal models and the control of animal environments depend on the establishment of strong scientific partnerships between research investigators and laboratory animal scientists. Laboratory animal care and use programs are becoming increasingly complex and are constantly changing, fueled in part by technological advances, changes in regulations concerning animal care and use, and economic pressures. Since the early 1980s, many institutions have moved to centralization of animal facility operations concomitant with numerous changes in housing systems, barrier concepts, equipment, and engineering controls of the macro- and microenvironment. These and other changes can have an impact on animals and the conduct of endocrine experiments. Despite the potential impact of animal care and use procedures on research endpoints, many investigators are surprisingly naive to the animal facility conditions that can affect in vivo studies. Several key animal care and use issues that are important to consider in endocrine experiments with rodent models are described.     

实验鼠群的健康监测管理

虽然实验鼠种群的总体健康水平得到了显著的提高,但还是有很多重要的传染性病原体在实验鼠群中流行.实验鼠群的健康状况对于动物福利、科学研究甚或人类健康都很重要.所以必须要对实验鼠群进行健康监测.笔者依据自身的实践和经验,对鼠群健康监测的基本原理进行了分析,包括以下的内容：鼠群健康监测的必要性、健康检测规程的建立、哨兵鼠、常用的监测力法、样本采集原则、对检测结果的解读和应对.相信读者在了解这些基本的原理后,能设定出符合自身设施实际的鼠群健康监测计划并逐步在实践中完善.     

Transgenic animal technology: alternatives in genotyping and phenotyping

Over the past decade, breakthrough technologies in transgenic animal technology and functional genomics have played a central role in the explosive growth of rodent modeling and in scientific innovation. Various noninvasive alternatives to routine surgical biopsy have been described for genotypic and phenotypic analyses of laboratory animals. A number of options are available to refine or replace potentially painful and invasive procedures ranging from tissue biopsies (including tail biopsies and toe docking) to several blood sampling techniques. Unfortunately, adoption of many non- or minimally invasive alternatives has proven difficult on a number of fronts ranging from historical reservations to procedural expectations and actual experimental productivity. Similarly, a variety of phenotyping considerations have addressed throughput efficiencies and the health and well being of research animals. From an animal welfare perspective, marked increases in laboratory animal populations have accompanied rapid advancements spanning the life sciences. As described for rodent modeling, but with applications across many laboratory animal species, diverse procedural refinements are available that will readily aid in the analysis of whole animal models. Ultimately, non-invasive technologies and complementary refinements have bearing on the quality and reproducibility of data that are reported, as well as of critical importance to the well being and ethical management of animals at all developmental stages: from fetal existence, to the neonatal period, and on through adulthood.     

Daily rhythms of Fos expression in hypothalamic targets of the suprachiasmatic nucleus in diurnal and nocturnal rodents.

Little is known about the differences in the neural substrates of circadian rhythms that are responsible for the maintenance of differences between diurnal and nocturnal patterns of activity in mammals. In both groups of animals, the suprachiasmatic nucleus (SCN) functions as the principal circadian pacemaker, and surprisingly, several correlates of neuronal activity in the SCN show similar daily patterns in diurnal and nocturnal species. In this study, immunocytochemistry was used to monitor daily fluctuations in the expression of the nuclear phosphoprotein Fos in the SCN and in hypothalamic targets of the SCN axonal outputs in the nocturnal laboratory rat and in the diurnal murid rodent, Arvicanthis niloticus. The daily patterns of Fos expression in the SCN were very similar across the two species. However, clear species differences were seen in regions of the hypothalamus that receive inputs from the SCN including the subparaventricular zone. These results indicate that differences in the circadian system found downstream from the SCN contribute to the emergence of a diurnal or nocturnal profile in mammals.     

New building, old parasite: Mesostigmatid mites--an ever-present threat to barrier facilities

Mesostigmatid mites are blood-sucking parasitic mites found in wild rodent populations. Periodically they can also become a problem for laboratory rodent colonies, particularly when building construction or renovations disturb colonies of commensal (building) rodents that had been acting as hosts. Mesostigmatid mites infest both rats and mice and, unlike the more common rodent fur mites (Myobia, Myocoptes, and Radfordia sp.), can survive for long periods in the environment and travel considerable distances in search of new hosts. They easily penetrate barrier caging systems, including individually ventilated cages, thus circumventing the usual precautions to protect rodents from infection. The two mites reported in laboratory rodent colonies, Ornithonyssus bacoti and Laelaps echidnina, also bite humans and have the potential to transmit zoonotic diseases. Once the mites gain access to a colony, eradication requires elimination of commensal rodent reservoirs in addition to insecticide treatment of both the laboratory rodents and the environment. In view of the undesirability of insecticide use in the animal facility, it is advisable to investigate the effectiveness of preventive treatments, such as environmental application of insect growth regulators or silica-based products. This article summarizes available information on mesostigmatid mites and their laboratory incursions, and provides suggestions for diagnosis, treatment, and control based on the authors experience with several outbreaks at a large academic institution..     

Pneumocystis: newer knowledge about the biology of this group of organisms in laboratory rats and mice

This review is an update on some of the remarkable advances that have led to greater understanding of Pneumocystis, an important group of rodent pathogens. The author outlines the life cycle of these pulmonic fungi, their taxonomic position, and their nomenclature. He discusses how infections begin and spread in laboratory rodent colonies, and how those infections are inadvertently maintained in barriered breeding colonies. He also addresses the diagnosis of Pneumocystis infection and provides suggestions for the establishment of Pneumocystis-free animal colonies.     

Clinical considerations in rodent bioimaging

Imaging modalities such as micro-computed tomography (micro-CT), micro-positron emission tomography (micro-PET), high-resolution magnetic resonance imaging (MRI), optical imaging, and high-resolution ultrasound are rapidly becoming invaluable research tools. These advanced imaging technologies are now commonly used to investigate rodent biology, metabolism, pharmacokinetics, and disease in vivo. Choosing an appropriate anesthetic regimen as well as monitoring and supporting the animal's physiologic balance is key to obtaining images that truly represent the biologic process or disease state of interest. However, there are many challenges in rodent bioimaging such as limited animal access, small sample volumes, anesthetic complications, strain and gender variability, and the introduction of image artifacts. Because each imaging study presents unique challenges, a thorough understanding of the imaging modality used, the animal's health status, and the research data desired is required. This article addresses these issues along with other common laboratory animal clinical considerations such as biosecurity and radiation safety in in vivo rodent bioimaging.     

Rodent laparoscopy: refinement for rodent drug studies and model development, and monitoring of neoplastic, inflammatory and metabolic diseases

The refinement of surgical techniques represents a key opportunity to improve the welfare of laboratory rodents, while meeting legal and ethical obligations. Current methods used for monitoring intra-abdominal disease progression in rodents usually involve euthanasia at various time-points for end of study, one-time individual tissue collections. Most rodent organ tumour models are developed by the introduction of tumour cells via laparotomy or via ultrasound-guided indirect visualization. Ischaemic rodent models are often generated using laparotomies. This approach requires a high number of rodents, and in some instances introduces high degrees of morbidity and mortality, thereby increasing study variability and expense. Most importantly, most laparotomies do not promote the highest level of rodent welfare. Recent improvements in laparoscopic equipment and techniques have enabled the adaptation of laparoscopy for rodent procedures. Laparoscopy, which is considered the gold standard for many human abdominal procedures, allows for serial biopsy collections from the same animal, results in decreased pain and tissue trauma as well as quicker postsurgical recovery, and preserves immune function in comparison to the same procedures performed by laparotomy. Laparoscopy improves rodent welfare, decreases inter-animal variability, thereby reducing the number of required animals, allows for the replacement of larger species, decreases expense and improves data yield. This review article compares rodent laparotomy and laparoscopic surgical methods, and describes the utilization of laparoscopy for the development of cancer models and assessment of disease progression to improve data collection and animal welfare. In addition, currently available rodent laparoscopic equipment and instrumentation are presented.     

Identification of bacterial strains by laboratories participating in the Deutsches Krebsforschungszentrum quality assurance programme

The quality assurance programme (QAP) of the Deutsches Krebsforschungszentrum (DKFZ) is a proficiency testing system developed to service the laboratory animal discipline. QAP comprises the quarterly distribution of two bacterial strains originating from various species of animals for identification to the species level and antibiotic susceptibility testing. We compared identification results reported by QAP participants over the years 1996-2004 with those obtained by the Dutch Bacterial Diagnostics reference laboratory on 68 samples comprising 71 bacterial strains and a fungus. Significant differences were found in the frequency of reported and correct identifications when bacteria were assigned to different groups based on morphology by Gram stain and on origin (animal versus environmental, rodent and rabbit versus other animal species, pathogen versus non-pathogens). Rodent and rabbit pathogens yielded 73% correct identifications, and with all bacterial strains only 60% of the identifications were correct. We assume that most QAP participants were from laboratory animal diagnostic laboratories. If this is true, the capabilities of laboratories in the laboratory animal discipline to correctly identify bacterial species are well below what are considered acceptable limits for human diagnostic laboratories. The distribution of cultured bacteria circumvents the most difficult step in the microbiological monitoring of animals, namely primary culture from clinical samples. We propose to set up a QAP that comprises the distribution of specimens mimicking clinical samples normally submitted to laboratory animal diagnostic laboratories.     

Genetically modified mouse health reporting: a need for global standardization

The distribution of GM mice between facilities has raised new problems because of variable microbiological quality. One of the most important management issues concerns the methods of reporting laboratory animal health surveillance results. The authors evaluated the format and content of 380 health reports of mice received from 55 institutions in Europe and North America. Their results suggest that a standardized rodent health form would facilitate the management of laboratory mouse distribution and infection control.     

Octodon degus: a diurnal, social, and long-lived rodent

Octodon degus is a moderate-sized, precocious, but slowly maturing, hystricomorph rodent from central Chile. We have used this species to study a variety of questions about circadian rhythms in a diurnal mammal that readily adapts to most laboratory settings. In collaboration with others, we have found that a number of fundamental features of circadian function differ in this diurnal rodent compared with nocturnal rodents, specifically rats or hamsters. We have also discovered that many aspects of the circadian system are sexually dimorphic in this species. However, the sexual dimorphisms develop in the presence of pubertal hormones, and the sex differences do not appear until after gonadal puberty is complete. The developmental timing of the sex differences is much later than in the previously studied altricial, rapidly developing rat, mouse, or hamster. This developmental timing of circadian function is reminiscent of that reported for adolescent humans. In addition, we have developed a model that demonstrates how nonphotic stimuli, specifically conspecific odors, can interact with the circadian system to hasten recovery from a phase-shift of the light:dark cycle (jet lag). Interestingly, the production of the odor-based social signal and sensitivity to it are modulated by adult gonadal hormones. Data from degu circadian studies have led us to conclude that treatment of some circadian disorders in humans will likely need to be both age and gender specific. Degus will continue to be valuable research animals for resolving other questions regarding reproduction, diabetes, and cataract development.     

筑巢材料在实验大、小鼠环境丰荣中的应用

相对于标准鼠盒,实验大、小鼠更喜好有筑巢材料的“环境丰荣”鼠盒.向标准鼠盒中放入筑巢材料,可以为大、小鼠提供筑巢、躲避、攀爬、休息的环境.因此,在实验大、小鼠饲养过程中,提供筑巢材料,是一个简单有效的丰富实验动物环境,提高实验动物福利的方法.本文就筑巢材料应用背景、近年来在啮齿类实验动物环境丰荣中的应用、对实验动物福利的影响三方面做以综述,并对今后筑巢材料在改善实验动物福利的应用前景作以展望.     

Nocturnal to Diurnal Switches with Spontaneous Suppression of Wheel-Running Behavior in a Subterranean Rodent

Several rodent species that are diurnal in the field become nocturnal in the lab. It has been suggested that the use of running-wheels in the lab might contribute to this timing switch. This proposition is based on studies that indicate feed-back of vigorous wheel-running on the period and phase of circadian clocks that time daily activity rhythms. Tuco-tucos (Ctenomys aff. knighti) are subterranean rodents that are diurnal in the field but are robustly nocturnal in laboratory, with or without access to running wheels. We assessed their energy metabolism by continuously and simultaneously monitoring rates of oxygen consumption, body temperature, general motor and wheel running activity for several days in the presence and absence of wheels. Surprisingly, some individuals spontaneously suppressed running-wheel activity and switched to diurnality in the respirometry chamber, whereas the remaining animals continued to be nocturnal even after wheel removal. This is the first report of timing switches that occur with spontaneous wheel-running suppression and which are not replicated by removal of the wheel.     

Antibiotic resistance in bacterial isolates from laboratory animal colonies naive to antibiotic treatment

Antiobiogrammes were made of a number of isolates of Staphylococcus aureus, Escherichia coli and Pasteurella pneumotropica derived from rodent, rabbit or minipig colonies never treated with antibiotics. For S. aureus no differences between rats and mice were found in the percentage of resistant isolates. Gentamicin and erythromycin were found to be the most efficient, while the highest percentages of resistance were found to be against penicillins and sulphonamides. In general, the results from antibiogrammes on E. coli were rather uniform, with only slight differences between isolates from different species, except that more vancomycin and tetracycline-resistant minipig isolates were found. In almost all isolates of E. coli, resistance was shown against penicillin, fucidin, macrolides, lincosamides and tiamulin. For a number of antibiotics, mouse isolates of P. pneumotropica were more frequently found to be sensitive than rat isolates. The resistance patterns of E. coli from the minipigs were quite similar to resistance patterns found in farm pigs, but apart from this, the resistance patterns of the bacterial species tested did not resemble human or farm animal patterns in any of the animal species, and, therefore, these studies do not support the theory that S. aureus and E. coli in laboratory animal colonies derive from the normal flora of the human caretakers. The fact that rodent species of E. coli, in contrast to human and farm animal species, are sensitive to ampicillin, tetracyclines, and the combination of sulphonamides and trimethoprim, might be due to the fact that these antibiotics are not used in rodent populations.     

Environmental enrichment of laboratory rodents: the answer depends on the question

Efforts to refine the care and use of animals in research have been ongoing for many years and have led to general standardization of rodent models, particularly with regard to animal housing, genetics, and health status. Concurrently, numerous informal practices and recommendations have been promulgated with the laudable intent of promoting general animal wellbeing through so-called enrichment of the cage environment. However, the variety of housing conditions fostered by efforts at environmental enrichment (EE) complicates the goal of establishing standardized or even defined environments for laboratory rodents. Many studies over the years have sought to determine whether or how various enrichment strategies affect the behavior and physiology of laboratory rodents. The findings, conclusions, and interpretations of these studies are mixed, particularly with regard to their application across rodent species, strains, genders, and ages; whether or how they affect the animals and the science; and, in some cases, whether the effects are positive, negative, or neutral in terms of animal wellbeing. Crucial issues related to the application of EE in research settings include its poorly defined effect on the animals, the potential for increased variability in the data, poor definition across labs and in publications, and potential for animal or scientific harm. The complexities, uncertainties, interpretational conundrums, varying conclusions, and lack of consensus in the EE literature warrant careful assessment of the benefits and liabilities associated with implementing such interventions. Reliance on evidence, professional judgment, and performance standards are crucial in the development of EE strategies.     

Seasonal variation of vocal behaviour in a temperate songbird: assessing the effects of laboratory housing on wild-caught, seasonally breeding birds

Many laboratories are conducting research using songbirds as their animal model. In particular, songbirds are widely used for studying the behavioural and neural mechanisms underlying vocal learning. Many researchers use wild-caught birds to conduct this research, although few studies of behaviour have been conducted to determine the effects of captive housing on these species. We investigated the vocal production pattern of wild-caught black-capped chickadees (Poecile atricapillus) over an entire season in laboratory housing. We documented the frequency of production of four vocalizations (fee-bee song, chick-a-dee calls, dee calls, and gargle calls) across seasons and diurnal pattern and compared the observed pattern of laboratory vocalizations to those previously observed and reported in the wild. Laboratory-housed chickadees had seasonal and diurnal vocal production shifts that were related to both photoperiodic changes (season) and diurnal pattern. For instance, there was significantly more fee-bee song in the spring than summer, autumn, and winter with the most fee-bee song occurring at spring dawn as seen in the wild. Our results also confirmed that the general pattern of vocalizations was consistent between wild and laboratory populations, with no significant differences for either the seasonal or diurnal pattern of fee-bee song production between populations. Differences between settings were observed in the pattern of chick-a-dee calls at dawn and sunset between field and laboratory populations. However, differences in the quantity of vocalization types between laboratory and wild populations suggest that housing conditions are influencing the normal vocal behavioural patterns.