Laboratory Mice Research Articles

Tuberculosis susceptibility in genetically diverse mice reveals functional diversity of neutrophils.

Tuberculosis (TB) is a heterogenous disease in humans with individuals exhibiting a wide range of susceptibility. This heterogeneity is not captured by standard laboratory mouse lines. We used a new collection of 19 wild-derived inbred mouse lines collected from diverse geographic sites to identify novel phenotypes during Mycobacterium tuberculosis ( Mtb ) infection. Wild derived mice have heterogenous immune responses to infection that result in differential ability to control disease at early timepoints. Correlation analysis with multiple parameters including sex, weight, and cellular immune responses in the lungs revealed that enhanced control of infection is associated with increased numbers of CD4 T cells, CD8 T cells and B cells. Surprisingly, we did not observe strong correlations between IFN-γ production and control of infection. Although in most lines high neutrophils were associated with susceptibility, we identified a mouse line that harbors high neutrophils numbers yet controls infection. Using single-cell RNA sequencing, we identified a novel neutrophil signature associated with failure to control infection.

Retrospective analysis on the occurrence of kidney cysts in mice in a central animal facility in the years 2009-2019.

Kidney cysts in humans are mainly caused by inheritable polycystic kidney disease. Although they are a regular finding in laboratory mice, their occurrence upon dissection has not been systematically investigated, yet. Therefore, the aim of this report was to investigate on prevalence, phenotype and aetiology of spontaneously occurring kidney cysts in mice by retrospectively analysing the laboratory-receipt tables of the in-house laboratory of a central animal facility in North Rhine-Westphalia, Germany, years 2009-2019. A percentage of 0.4% of dissected mice displayed kidney cysts, with more male than female animals affected and average age equal to that of all dissected animals. Preliminary report in half of the cases was distended abdomen, and a few individuals displayed additional pathologic alterations of kidneys, most commonly dilated renal pelvis, or extrarenal comorbidities. Kidney cysts occurred independently of a renal phenotype of the transgenic strain or presence of infectious agents in health monitoring. To conclude, kidney cysts were characterized as harmless for affected mice but, as inheritability is suggested according with the literature, affected animals should be excluded from breeding.

Effect of dietary phospholipid on the behavior in C57BL/6J mice

Nowadays phospholipids are widely used as hepatoprotective, neuroprotective and anti-stress drugs, as well as the dietary supplements. Besides, lecithin consisting up to 70% of the phospholipids mixture: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidic acid, is the often component of food production as an emulsifier. Dose of these biologically active substances in the modern human diet could be quite high. Previously we have shown that chronic intestinal inflammation in Muc2-knockout mice induces behavioral changes along with the significant increase in the content of phospholipids in intestinal epithelial cells, particularly, phosphatidylcholine, phosphatidylserine and phosphatidic acid. Here we investigate the effects of long-term administration of a mixture of these phospholipids, as well as the effects of long-term administration of soy lecithin on the behavioral patterns in laboratory mice. Animals long-term taken a phospholipid mixture shows no normally observed preference towards females in the two intruders test (with female and male). In the social odor preference test, they also did not distinguish female and male odors, while non-social odors discrimination preserved. In addition, we identified a decrease in anxiety, obsessive traits, and schizophrenia-like behavior traits in these animals. Soy lecithin supplementation had similar effects on social behavior and compulsive traits, and increased aggression in males. Thus, long-term perinatal administration of either mixture of phospholipids (phosphatidylcholine, phosphatidylserine and phosphatidic acid) or soy lecithin can influence various aspects of behavior in mice.

Study of the cyto- and genotoxic activity of water from the Kapshagai reservoir (Kazakhstan) on laboratory mice

Chemical compounds in the environment, which exhibit toxic and genotoxic activity, increase the mutational pressure on biota. This study aimed to investigate the genotoxic, mutagenic, and toxic effects of water from the Ile River and the Kapshagai Reservoir, both sites of active economic activities. Cytogenetic analysis of bone marrow from mice exposed to water samples from the Ile River and the Kapshagai Reservoir revealed a statistically significant increase in aberrant (p<0.05) and polyploid cells (p<0.01), as well as a decrease in the mitotic index (p<0.001), compared to the negative control. The water samples caused statistically significant increases in single- and double-strand DNA breaks in cells across various organs in the experimental mice compared to unexposed animals (p<0.001). These observations suggest the existence of chemical compounds within the water samples from the Kapshagai Reservoir and the Ile River, which exhibit genotoxic, mutagenic, and toxic properties.

Squamates as a model to understand key dental features of vertebrates

Thanks to their exceptional diversity, teeth are among the most distinctive features of vertebrates. Parameters such as tooth size, shape, number, identity, and implantation can have substantial implications for the ecology and certain social behaviors of toothed species. Despite decades of research primarily focused on mammalian dentition, particularly using the laboratory mouse model, squamate reptiles (“lizards” and snakes) offer a wide array of tooth types and dentition variations. This diversity, which includes differences in size, shape, function, and replacement capacity, provides invaluable opportunities for investigating these fundamental properties. The central bearded dragon (Pogona vitticeps), a popular pet species with well-established husbandry practices, is of particular interest. It features a broad spectrum of morphs and spontaneous mutants and exhibits a wide range of heterodont phenotypes, including variation in the size, shape, number, implantation, and renewal of teeth at both posterior and anterior positions. These characteristics position the species as a crucial model organism for developmental studies in tooth research and for gaining deeper insights into evolutionary patterns of vertebrate dentitions. In this article, we provide an overview of the current understanding of squamate dentition, its diversity, development, and replacement. Furthermore, we discuss the significant advantages offered by squamate species as model organisms for investigating the evolutionary and developmental aspects of vertebrate dentition.

Bacteriophage-driven emergence and expansion of Staphylococcus aureus in rodent populations.

Human activities such as agriculturalization and domestication have led to the emergence of many new pathogens via host-switching events between humans, domesticated and wild animals. Staphylococcus aureus is a multi-host opportunistic pathogen with a global healthcare and economic burden. Recently, it was discovered that laboratory and wild rodents can be colonised and infected with S. aureus, but the origins and zoonotic potential of rodent S. aureus is unknown. In order to trace their evolutionary history, we employed a dataset of 1249 S. aureus genome sequences including 393 of isolates from rodents and other small mammals (including newly determined sequences for 305 isolates from 7 countries). Among laboratory mouse populations, we identified multiple widespread rodent-specific S. aureus clones that likely originated in humans. Phylogeographic analysis of the most common murine lineage CC88 suggests that it emerged in the 1980s in laboratory mouse facilities most likely in North America, from where it spread to institutions around the world, via the distribution of mice for research. In contrast, wild rodents (mice, voles, squirrels) were colonized with a unique complement of S. aureus lineages that are widely disseminated across Europe. In order to investigate the molecular basis for S. aureus adaptation to rodent hosts, genome-wide association analysis was carried out revealing a unique complement of bacteriophages associated with a rodent host ecology. Of note, we identified novel prophages and pathogenicity islands in rodent-derived S. aureus that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes promoting survival in new host-species.

The effect of food timing on torpor propensity and characteristics in laboratory mice during a common food restriction paradigm

Background Many behavioural, pharmacological, and metabolic studies in mice require fasting, yet the possibility of fasting-induced torpor affecting the data is rarely considered. Torpor is a state characterised by depressed metabolism and profound alterations to physiology and behaviour. In this study we aimed to determine how the effects of torpor on experimental outcomes could be mitigated. Methods To this end, timing and characteristics of fasting-induced torpor in response to feeding in the morning versus feeding in the night were compared using non-invasive monitoring of peripheral body temperature. Results Night-fed mice entered significantly more torpor bouts per day compared to morning-fed mice (Morning: 2.79±0.197 (mean ± SEM); Night: 4.79±0.533 (mean ± SEM); p=0.0125), but these bouts were shorter on average by ~1.5h. Latency to the first torpor bout following feeding tended to be shorter during night feeding (Morning: 9.57±0.8h (mean ± SEM); Night: 6.66±1.2h (mean ± SEM); p=0.0928). Moreover, torpor bouts typically occurred during the dark phase in the morning-fed group, whilst night feeding resulted in a shift of torpor occurrence to earlier in the day (Morning: 14.2±0.4 ZT h (mean ± SEM); Night: 12.2±0.9 ZT h (mean ± SEM); p=0.0933). There was a high degree of variation in torpor occurrence within and between animals in each group. Conclusions We recommend that feeding time is kept consistent between days and the same across animals to minimise variation in torpor occurrence. Moreover, the timing of food provision may be optimised to allow measurements to be taken during euthermia, to mitigate the effects of torpor on the variables investigated. Finally, we recommend that body temperature is monitored non-invasively to determine when torpor is occurring, and that testing, or sample collection is conducted when the torpor history is comparable between animals.

Comparative reservoir competence of Peromyscus leucopus, C57BL/6J, and C3H/HeN for Borrelia burgdorferi B31.

Borrelia burgdorferi, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed deermouse Peromyscus leucopus, is reported not to have reduced fitness following infection. Although laboratory strains of Mus musculus mice have successfully been leveraged to model acute human Lyme disease, the ability of these rodents to model B. burgdorferi-P. leucopus interactions remains understudied. Here, we compared infection of P. leucopus with B. burgdorferi B31 with infection of the traditional B. burgdorferi murine models-C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that B. burgdorferi was able to reach much higher burdens (10- to 30-times higher) in multiple M. musculus skin sites and that the overall dynamics of infection differed between the two rodent species. We also found that P. leucopus remained transmissive to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and rodent-to-tick transmission in these hosts. Similarly, we also observe evidence of inflammation in infected P. leucopus hearts. These observations provide new insight into reservoir species and the B. burgdorferi enzootic cycle.IMPORTANCEA Lyme disease-causing bacteria, Borrelia burgdorferi, must alternate between infecting a vertebrate host-usually rodents or birds-and ticks. In order to be successful in that endeavor, the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work, we examine how B. burgdorferi and one of its primary vertebrate reservoirs, Peromyscus leucopus, interact during an experimental infection. We find that B. burgdorferi appears to colonize its natural host less successfully than conventional laboratory mouse models, which aligns with a sustained seemingly anti-bacterial response by P. leucopus against the microbe. These data enhance our understanding of P. leucopus host-pathogen interactions and could potentially serve as a foundation to uncover ways to disrupt the spread of B. burgdorferi in nature.

A simple method for repeated in vivo sperm collection from laboratory mice

PurposeMouse spermatozoa for archiving laboratory mice or for in vitro fertilization (IVF) are routinely obtained from the cauda epididymis of adult males sacrificed for this purpose. To avoid the death of the donor, we tested whether a precisely timed interruption of the mating act could be used for repeated sperm collection from laboratory mice.MethodsSperm donors (B6D2F1) were mated with a receptive female, and mating behavior was observed. The stud was separated from the female 1–2 s after the onset of the ejaculatory shudder. The ejected copulatory plug with the yellowish viscous ejaculate was carefully removed from the penile cup.ResultsA total of 80 ejaculates were successfully obtained from 100 ejaculations. The latency to first mount was 1.1 ± 1.1 min (mean ± SD) and to ejaculation 8.1 ± 4.7 min. The average number of mounts to ejaculation was 10.5 ± 5.8, and the mean number of spermatozoa per collected ejaculate was 1.86 ± 1.05 × 106. An average fertilization rate of 76% was observed after IVF.ConclusionsSeparating the stud from the female just before ejaculation is feasible, easy to learn, and requires no special equipment. The sperm count of collected ejaculates is lower than natural ejaculations, but higher than previous in vivo sperm collection methods achieved. We recommend this simple sperm collection method in mice, especially when the donor cannot be sacrificed and/or repeated sperm collection from the same animal is required for experimental purposes.

Assessment of the impact of physical and chemical factors of the production environment on the morphological state of target organs in an animal experiment

The study of the morphological state of target organs of outbred (nonlinear) laboratory mice ICR (CD-1), which were under prolonged dynamic influence of physical and chemical factors of the production environment under model conditions, is of wide research interest, as it allows to assess the impact of these factors at the tissue and cellular level and to identify the presence of pathological changes in relation to the group control that was not exposed to the studied factors of the production environment during the 90-day experiment, which has clinical and practical significance. When assessing the 90-day dynamics (from 0 days – 6 months (background) to 30–60–90 days – 7–8–9 months) of the impact of environmental factors on the morphological state of tissues and organs of outbred (nonlinear) laboratory mice ICR (CD-1), generally accepted and unified methods were used. Animals (weighing 45–50 gr., sexually mature age – 6 months) were divided into 3 experimental groups (vibration exposure, noise exposure, chemical exposure) of 30 individuals each (15 females and 15 males) and 1 control group (15 females and 15 males), kept in standard comfortable conditions, and not exposed to the factors of the production environment. The experiment was conducted in accordance with the rules adopted by the European Convention for the Protection of Animals Used for Experimental Scientific Purposes (Strasbourg, 1986), after approval by the Ethical commission of the Novosibirsk Research Institute of Hygiene of Rospotrebnadzor. Statistical processing of the research materials was carried out using standard Statistica 10.0 application programs. The morphological analysis of the target organs of experimental animals revealed the presence of a complex of pathological changes in the 90-day dynamics of the impact of factors of the production environment, compared with the morphological state of the organs in the control group. The results obtained have clinical and practical significance, as they allow us to justify preventive measures aimed at preventing the negative impact of long-term production factors on the labor contingent. Further study of the morphological state of target organs of ICR laboratory mice exposed to prolonged dynamic exposure to physical and chemical factors of the production environment under model conditions will contribute to the establishment of mechanisms for the development of occupational diseases and the development of scientifically based medical and hygienic measures aimed at preserving the health of the labor contingent in the management of labor longevity.

The mouse Social Frailty Index (mSFI): a novel behavioral assessment for impaired social functioning in aging mice.

Various approaches exist to quantify the aging process and estimate biological age on an individual level. Frailty indices based on an age-related accumulation of physical deficits have been developed for human use and translated into mouse models. However, declines observed in aging are not limited to physical functioning but also involve social capabilities. The concept of "social frailty" has been recently introduced into human literature, but no index of social frailty exists for laboratory mice yet. To fill this gap, we developed a mouse Social Frailty Index (mSFI) consisting of seven distinct assays designed to quantify social functioning which is relatively simple to execute and is minimally invasive. Application of the mSFI in group-housed male C57BL/6 mice demonstrated a progressively elevated levels of social frailty through the lifespan. Conversely, group-housed females C57BL/6 mice manifested social frailty only at a very old age. Female mice also showed significantly lower mSFI score from 10months of age onward when compared to males. We also applied the mSFI in male C57BL/6 mice under chronic subordination stress and in chronic isolation, both of which induced larger increases in social frailty compared to age-matched group-housed males. Lastly, we show that the mSFI is enhanced in mouse models that show accelerated biological aging such as progeroid Ercc1-/Δ and Xpg-/- mice of both sexes compared to age matched littermate wild types. In summary, the mSFI represents a novel index to quantify trajectories of biological aging in mice and may help elucidate links between impaired social behavior and the aging process.

Microglia undergo molecular and functional adaptations to dark and light phases in male laboratory mice

Microglia are increasingly recognized to contribute to brain health and disease. Preclinical studies using laboratory rodents are essential to advance our understanding of the physiological and pathophysiological roles of these cells in the central nervous system. Rodents are nocturnal animals, and they are mostly maintained in a defined light–dark cycle within animal facilities, with many laboratories investigating the molecular and functional profiles of microglia exclusively during the animals’ light (sleep) phase. However, only a few studies have considered possible differences in microglial functions between the active and sleep phases. Based on initial evidence suggesting that microglial intrinsic clock genes can affect their phenotypes, we sought to investigate differences in transcriptional, proteotype and functional profiles of microglia between light (sleep) and dark (active) phases, and how these changes are affected in pathological models. We found marked transcriptional and proteotype differences between microglia harvested from male mice during the light or dark phase. Amongst others, these differences related to genes and proteins associated with immune responses, motility, and phagocytosis, which were reflected by functional alterations in microglial synaptic pruning and response to bacterial stimuli. Possibly accounting for such changes, we found RNA and protein regulation in SWI/SNF and NuRD chromatin remodeling complexes between light and dark phases. Importantly, we also show that the time of microglial sample collection influences the nature of microglial transcriptomic changes in a model of immune-mediated neurodevelopmental disorders. Our findings emphasize the importance of considering diurnal factors in studying microglial cells and indicate that implementing a circadian perspective is pivotal for advancing our understanding of their physiological and pathophysiological roles in brain health and disease.

Effects of temporary access to environmental enrichment on measures of laboratory mouse welfare

Laboratory mice are typically housed in “shoebox” cages with limited opportunities to engage in natural behaviour. Temporary access to environments with increased space and complexity (playpens) may improve mouse welfare. Previous work by our group has shown that mice are motivated to access and use these environments, but it is unknown how other aspects of welfare are impacted. Female C57BL/6J, BALB/cJ, and DBA/2J mice (n = 21; 7 mice per strain) were housed in mixed-strain trios and given temporary access to a large playpen with their cage mates three times per week. Control mice (n = 21; 7 mice per strain) remained in their home cages. Home cage behaviour (development of stereotypic behaviour over time, aggression following cage-changing) and anxiety tests were used to assess how playpen access impacted welfare. Contrary to our predictions, we found increased time spent performing stereotypies in playpen mice; this difference may be related to negative emotional states, increased motivation to escape the home cage, or active coping strategies. Playpen access resulted in strain-dependent improvements in aggression and some measures of anxiety. Aggression was lower for C57BL/6J mice in the playpen treatment following cage changing than it was for C57BL/6J control mice, while playpen mice, and particularly the C57BL/6J strain, spent more time in the center of the open field test and produced fewer fecal boli during anxiety testing, supporting other research showing that strain differences play an important role in behaviour and stress resiliency.

Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home-Cage Behavior.

Lafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age-dependent manner in all mouse models of LD. In this study, we applied home-cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin-deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6-7 months, and ∼12 months of age, malin-deficient mice ("KO") and wild-type (WT) littermates underwent a standardized home-cage behavioral assessment designed to non-obtrusively appraise features of rest/arousal, consumptive behaviors, risk aversion, and voluntary wheel-running. At all timepoints, and over a range of metrics that we report transparently, WT and KO mice were essentially indistinguishable. In contrast, within WT mice compared across the same timepoints, we identified age-related nocturnal hypoactivity, diminished sucrose preference, and reduced wheel-running. Neuropathological examinations in subsets of the same mice revealed expected age-dependent LB accumulation, gliosis, and microglial activation in cortical and subcortical brain regions. At 12 months of age, despite the burden of neocortical LBs, we did not identify spontaneous seizures during an electroencephalographic (EEG) survey, and KO and WT mice exhibited similar spectral EEG features. However, in an in vitro assay of neocortical function, paroxysmal bursts of network activity (UP states) in KO slices were more prolonged at 3 and 6 months of age, but similar to WT at 12 months. KO mice displayed a distinct response to pentylenetetrazole, with a greater incidence of clonic seizures and a more pronounced postictal suppression of movement, feeding, and drinking behavior. Together, these results highlight the clinicopathologic dissociation in a mouse model of LD, where the accrual of LBs may latently modify cortical circuit function and seizure threshold without clinically meaningful changes in home-cage behavior. Our findings allude to a delay between LB accumulation and neurobehavioral decline in LD: one that may provide a window for treatment, and whose precise duration may be difficult to ascertain within the typical lifespan of a laboratory mouse.

Mechanisms of biological effectiveness of ionic forms of metals of variable valence in respiratory medicine

Background: The task to develop new drugs containing metals of variable valence requires systematization of our knowledge, experimental and clinical studies. The aim of the study: To investigate the mechanisms of the effectiveness of the mineral complex containing metals of variable valence in the treatment of respiratory diseases, to conduct preclinical trials and clinical testing of a new inhalation mineral solution. Materials and methods: The ability of cerium (III) ions to exhibit reducing properties was demonstrated by carrying out chemical reactions of cerium (III) chloride and sulfate with potassium permanganate in the presence of sodium hydroxide or sulfuric acid (respectively). Preclinical studies of acute toxicity were carried out on laboratory mice and rats in accordance with the rules of bioethics and with generally accepted ethical standards for the treatment of animals, based on the standard operating procedures of the university, which comply with the rules adopted by the European Convention for the Protection of Vertebrate Animals used for research and other scientific purposes (Strasbourg, 1986). Clinical testing of two forms of the mineral complex for inhalation (1. Inhalation solution for nebulizer – Renerium; 2. intranasal spray) was carried out on 6 groups of volunteers in compliance with human rights and the principles of conducting medical research involving a person as a subject, declared on the 18th General Assembly of the World Medical Association (Helsinki, Finland), voluntary informed consent, approved by the local ethical committee. Results: Mineral preparation for inhalation therapy of patients with acute respiratory diseases does not show acute toxicity in preclinical studies on laboratory animals. The mechanism of action of the drug is most likely associated with the regulation of redox reactions at the level of the cell membrane, mitochondria and cell nucleus, which is manifested by anti-inflammatory and regenerative activity in the mucous membrane of the respiratory tract and alveolar apparatus. Both forms of the drug are well tolerated. A pronounced clinical efficacy of the drug Renerium in the form of inhalation through a compressor inhaler was noted in the case of a 5-day course of treatment, 5 ml once a day. Conclusion: Experimental and clinical data have demonstrated pronounced anti-inflammatory and regenerative properties of a new mineral complex based on cerium (III), the mechanism of which is due to the regulation of redox reactions.

The Brain-Heart Network of Syncope.

Observed and recorded in various forms since ancient times, 'syncope' is often popularly called 'fainting', such that the two terms are used synonymously. Syncope/fainting can be caused by a variety of conditions, including but not limited to head injuries, vertigo, and oxygen deficiency. Here, we draw on a large body of literature on syncope, including the role of a recently discovered set of specialized mammalian neurons. Although the etiology of syncope still remains a mystery, we have attempted to provide a comprehensive account of what is known and what still needs to be performed. Much of our understanding of syncope is owing to studies in the laboratory mouse, whereas evidence from human patients remains scarce. Interestingly, the cardioinhibitory Bezold-Jarisch reflex, recognized in the early 1900s, has an intriguing similarity to-and forms the basis of-syncope. In this review, we have integrated this minimal model into the modern view of the brain-neuron-heart signaling loop of syncope, to which several signaling events contribute. Molecular signaling is our major focus here, presented in terms of a normal heart, and thus, syncope due to abnormal or weak heart activity is not discussed in detail. In addition, we have offered possible directions for clinical intervention based on this model. Overall, this article is expected to generate interest in chronic vertigo and syncope/fainting, an enigmatic condition that affects most humans at some point in life; it is also hoped that this may lead to a mechanism-based clinical intervention in the future.

An ethically guided preclinical device for phenotyping H2 production in laboratory rodents.

Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance. This study proposes an innovative solution to accurately monitor H2 production in free-moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1-h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first-order moving average. HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s-1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s-1 for animals under control diet and 1.99 nmol.s-1 for animals under inulin diet. The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.

Shape variation in cranium, mandible and teeth in selected mouse strains.

There are different strains of laboratory mouse used in many different fields. These strains differ anatomically. In order to determine these anatomical differences, shape analysis was conducted according to species. CD-1, C57bl/6 and Balb-c strains were preferred to study these differences. Forty-eight adult mouse strains belonging to these strains were utilized. The bones were photographed and geometric morphometry was applied to these photographs. Principal Component Analysis was applied to determine shape variations. In Principal component 1 for cranium, CD-1 and C57bl/6 strain groups showed different shape variations, while Balb-c strain group showed similar shape variations to the other strain groups. Principal Component 1 for the mandible separated the CD-1 and C57bl/6 strain groups in terms of shape variation. Principal Component 2 explained most of the variation between the C57bl/6 and CD-1 lineage groups. In PC1 for molars, the CD-1 group showed a different shape variation from the other groups. Mahalanobis distances and Procrustes distances were measured using Canonical variance analysis to explain the differences between the lineage groups. These measurements were statistically significant. For cranium, in canonical variate 1, CD-1 group of mouse and Balb-c group of mouse were separated from each other. In canonical variate 2, C57bl/6 group of mouse were separated from the other groups. For mandible, Balb-c group of mouse in canonical variate 1 and CD-1 group of mouse in canonical variate 2 were separated from the other groups. For molars, CD-1 group of mouse in canonical variate 1 and Balb-c group of mouse in canonical variate 2 were separated from the other groups. It was thought that these anatomical differences could be caused by genotypic factors as well as dietary differences and many different habits that would affect the way their muscles work.

Lockbox enrichment facilitates manipulative and cognitive activities for mice

Background Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing and super-environmental enrichment. Methods Young adult female C57BL/6JCrl mice were examined before and after 2-month exposure to the different types of enrichment in a phenotyping test battery, including tests for trait and state anxiety-related behavior, calorimetric measurements, body weight measurements, and the analysis of stress hormone metabolite concentrations as well as sequential problem-solving abilities. At the end of the study, adrenal gland weights were determined and pathohistological evaluation was performed. For all continuous variables, the relative variability was calculated. Results We demonstrated that lockbox enrichment decreased trait anxiety-related behavior compared to conventional housing in the Grid Exploratory Paradigm. In contrast, the different types of enrichment neither influenced state anxiety-related behavior in the Open Field and Elevated Plus Maze Test nor physiological variables (i.e., bodyweight, resting metabolic rate, stress hormone metabolite concentrations, and adrenal gland weights). Lockbox enrichment improved sequential problem-solving when compared to super-environmental enrichment. Regardless of the housing condition, the relative variability increased in most variables over time, although the coefficient of variation decreased for some variables, especially in animals with access to the lockbox enrichment. A pathohistological evaluation revealed no evidence of toxicopathological effects associated with the material from which the lockbox enrichment was made. Conclusions Overall, the lockbox enrichment revealed beneficial effects on the affective state and sequential problem-solving abilities of laboratory mice. The reproducibility was demonstrated not to be compromised by lockbox enrichment, similar to super-environmental enrichment.

Effects of Silver Citrate Prolonged Exposure on Behavioral and Cognitive Functions of Mice

Pure silver as well as silver compounds have been used as antiseptics for centuries. Nowadays, the most frequently applied silver compounds are silver nanoparticles. Several studies demonstrate the ability of silver nanoparticles and silver salts to accumulate in the brain of laboratory animals as well as the ability of silver nanoparticles to influence behavioral and cognitive functions of laboratory mammals. For the first time, the influence of silver citrate on the change dynamics of behavioral and cognitive functions of laboratory mice at the daily oral exposure during 30, 60, 120, and 180 days were investigated in the present research. We observed the anxiety increase after 30 days of the exposure as well as the ability of mice to adapt to the prolonged oral exposure of silver citrate manifested in the anxiety decrease, increase of locomotor activity and the tendency of long-term contextual memory improvement at the further stages of the experiment. Increase of locomotor activity and memory improvement might be associated with the sensitivity increase and regarded as compensatory mechanism to anxiety increase. The observed phenomenon is classified as a hormetic effect. A comparison with the analogous study, which implemented polyvinylpyrrolidone coated silver nanoparticles, is carried out. It was concluded that the nanoscale impacts into the toxicity of silver compound.