Experimental Animals最新文献

Rats were the first mammals to be domesticated for scientific research, and abundant physiological data are available on them. Rats are expected to continue to play an important role as experimental animals, especially with advancements such as CRISPR/Cas9 technology. Environmental enrichment aims to promote species-specific behaviors and psychological well-being. In the present study, we designed a double-decker (DD) cage, which utilizes two stacked plastic cages for rat enrichment, and investigated the influence of housing in the DD cage on rat mating behavior. The results indicated that mount frequency, total mount counts, and total ejaculation latency were significantly lower in the DD cages than in the single-decker (SD) cages. Notably, in the DD cages, the body weight loss of male rats after mating behavior was lower than that observed in the SD cage. Water consumption per day during mating behavior was also significantly lower in the DD cages, although no significant differences were observed in daily food intake during mating behavior. In addition, reproductive performance, including pregnancy rate and birth rate, did not change in the DD cages. In summary, our study demonstrated that DD cages reduce mount frequency and ejaculation latency during rat mating, resulting in decreased water consumption and weight loss in male rats. Therefore, housing in DD cages may serve as a beneficial enrichment for rats.

The complement active product, C3a, and the receptor C3aR comprise an axis that exerts various biological functions, such as protection against infection. C3a is highly expressed in the inflamed skin and blood from patients with psoriasiform dermatitis. However, the role of the C3a/C3aR axis in psoriasiform dermatitis remains unclear because conflicting results using C3^-/- mice have been published. In this study, to elucidate the contribution of commensal microbiota in C3^-/- and wild-type (WT) mice were subjected to imiquimod-induced psoriasiform dermatitis under different housing conditions. C3^-/- mice showed increased epidermal thickness and keratinocyte proliferation markers in the inflamed ear compared to WT mice upon treatment with IMQ. These inflamed phenotypes were observed in both cohoused and separately housed conditions, and antibiotic treatment did not abolish the aggravation of IMQ-induced psoriasiform dermatitis in C3^-/- mice. These results suggested that the difference of commensal microbiota is not important for the C3-involved psoriasiform dermatitis. Keratinocyte hyperproliferation is a major feature of the inflamed skin in patients with psoriasiform dermatitis. In vitro experiments showed that C3a and C3aR agonists inhibited keratinocyte proliferation, which was abolished by introduction of a C3aR antagonist. Collectively, these results suggest that the C3a/C3aR axis plays a critical role in psoriasiform dermatitis development by inhibiting keratinocyte proliferation, regardless of the regulation of the commensal microbiota.

Acupuncture has obvious therapeutic effect on intracerebral hemorrhage (ICH). miR-34a-5p regulated by acupuncture was found to attenuate neurological deficits in ICH. However, the underlying mechanisms are unclear. Ubiquitin-like 4A (UBL4A) has not been studied in ICH. SD rats were injected with autologous blood to induce ICH and treated with Baihui-penetrating-Qubin acupuncture. Acupuncture resulted in an increase in forelimb placing test scores, and a decrease in corner test scores and brain water content of ICH rats. Histopathological examination showed that acupuncture inhibited ICH-induced inflammation, decreased damaged neurons and increased UBL4A expression. UBL4A overexpression increased cell viability, inhibited apoptosis, reduced reactive oxygen species (ROS) level and increased manganese superoxide dismutase (MnSOD) activity, mitochondrial membrane potential and mtDNA level in rat embryonic primary cortical neurons. miR-34a-5p knockdown increased UBL4A expression, apoptosis rate and ROS level in hemin-treated neurons. Dual luciferase assays showed that miR-34a-5p bound to UBL4A. Apoptotic cells and ROS level were increased in hemin-treated neurons with UBL4A and miR-34a-5p knockdown. We firstly demonstrate the inhibitory effect of UBL4A on neuronal apoptosis, and the regulation relationship between UBL4A and miR-34a-5p. This study provides a new candidate target for ICH treatment and more basis for elucidating the molecular mechanism of acupuncture. In the future, we will conduct a deeper exploration of the effects of UBL4A on ICH.

Allele-specific, monoallelic expression in diploid organisms represents an extreme case of allelic imbalance resulting from incompatibility between cis- and trans-elements. Due to haploinsufficiency, such monoallelic expression can lead to sporadic genetic diseases. In mice, allelic imbalances can be introduced into F1 offspring from inbred strains. Previously, we established F1 hybrid embryonic stem (ES) cell lines derived from four different mouse strains, each belonging to a different subspecies with substantial genetic polymorphisms. In this study, we investigated the neural differentiation capacity of the established ES cell lines. By introducing different culture conditions, which kept the ES cells undifferentiated under various pluripotencies, we succeeded in differentiating the majority of ES cell lines (eight out of eleven) with our default neural differentiation paradigm. Still, three lines exhibited insufficient differentiation despite combining culture conditions promoting undifferentiated as well as differentiated status. In addition, Ube3a imprinting was seen in two lines. Our findings contribute to the methodological understanding of mouse ES cell pluripotency and lead to the practical utility of F1 hybrid ES cells as a model for studying phenotypes resulting from gene locus interactions.

Here, we report the identification of causative genes for limb-shortening in individuals repeatedly found in a population of severely immunodeficient NOG mice maintained via sibling mating. First, we conducted a pedigree survey to determine whether limb-shortening was a recessive genetic trait and then identified it using a crossing test. Simultaneously, the symptoms were identified in detail using pathological analysis. Accordingly, a mouse strain exhibiting a recessive trait caused by a single gene trait and similar symptoms was identified, suggesting growth differentiation factor 5 (Gdf5) as a causative gene. Genome walking via PCR and sequence analysis of Gdf5 revealed a deletion of approximately 1.1 kb from the latter half of exon 2 of Gdf5. Furthermore, we established NOG-Gdf5^bpJic by removing other modified genes and confirmed that the inheritance pattern was reconfirmed semi-dominant. In recent years, regenerative medicine research using immunodeficient mice has been actively conducted, and this murine strain is expected to contribute to niche stem cell analysis and transplantation research.

Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been an integral part of an anti-obesity therapeutic regimen. To examine the relationship between anti-obesity and sleep, we explored the effect of MSE on sleep structure in high-fat diet (HFD)-induced obese mice. Although HFD did not alter the total amount of daily sleep, it significantly reduced the average duration of non-rapid eye movement (NREM) sleep and wakefulness episodes and significantly increased the number of these episodes. These findings indicate fragmented NREM sleep due to repeated brief awakenings in the HFD-fed mice. When 1% (w/v) MSE was given to HFD-fed mice, their weight or sleep structure were comparable to those of ND-fed mice, proving that dietary MSE completely hindered HFD-induced weight gain and sleep/wake fragmentation. Our data provide compelling evidence that MSE is a novel and promising dietary supplement that restores obesity-induced sleep architecture changes in mice.

Sepsis-induced acute lung injury represents a significant threat to human health and is frequently associated with pulmonary thrombosis due to dysregulation of the coagulofibrinolytic system. Plasmin, the major protease that degrades fibrin aggregates, is activated predominantly by tissue-plasminogen activator (tPA), whereas tPA is negatively regulated by plasminogen activator inhibitor (PAI-1). Under septic conditions, the imbalance between coagulation and fibrinolysis results in excessive microthrombosis. Pulmonary capillary endothelial cells serve as a primary source of tPA and PAI-1. The molecular pathways regulating their expression levels depend on the differential activity of transcription factors. In this study, we elucidated the role of the zinc-finger transcription factor GATA3 in response to sepsis-induced pulmonary embolism. Endothelial cell-specific GATA3-deficient mice (G3-ECKO) presented increased susceptibility to bacterial endotoxin-induced pulmonary embolism, which was associated with increased PAI-1 expression levels and decreased tPA expression levels in the lungs. Septic lung extracts from G3-ECKO mice consistently presented decreased plasmin activity, which likely underlies the increased coagulation. These results demonstrate that GATA3 plays a protective role against bacterial endotoxin-induced pulmonary vascular embolism. Our findings will contribute to understanding the molecular mechanisms involving GATA3 in preventing pulmonary embolism.

Hamsters are valuable rodent models that are distinct from mice and rats. Currently, the main hamster species used for experimental research are the Syrian golden hamster and Chinese hamster, in addition to hamster species from other countries. Chinese hamsters are small, easy to run and feed, and inexpensive. They are prominent species found only in China and are part of the experimental animal resources of Chinese specialty. Chinese hamsters are distinguished by a black stripe on their back, short tail, pair of easily retractable cheek pouches, and pair of large drooping testes in males with 22 chromosomes. Due to their unique anatomical structure and biological features, Chinese hamsters have been used as a model in biomedical research. Moreover, the breeding and use of Chinese hamsters was comprehensively studied in 1958, with significant breakthroughs. We present a thorough review of the current developments and applications of Chinese hamsters and support the use of this species as a suitable and innovative experimental research model. With the success of Chinese hamster transgenic technology, this species will become more commonly employed in biological and medical research in the future.

Physiological responses to inhaled anesthetics vary among species. Therefore, a precise anesthetic technique is important for each individual species. In this study, we focused on the degu (Octodon degus), a small herbivorous rodent. Degus have recently begun to be used as laboratory models for brain research because of certain human-like characteristics, such as spontaneous development of Alzheimer's disease. In this study, we evaluated appropriate induction and maintenance anesthesia conditions for isoflurane and sevoflurane in degus by a stimulation test, electroencephalography (EEG), minimum alveolar concentration (MAC), and vital signs. During induction, more rapid time to loss of the righting reflex and deeper anesthesia in degus were observed in isoflurane. The MAC value for degus were 1.75 ± 0.0% in isoflurane and 2.25 ± 0.27% in sevoflurane. Whereas some degus were awake during maintenance anesthesia using both anesthetics at concentrations of ≤2%, no rats were awake when using sevoflurane at a concentration of 2%. The duration of the total flat EEG, a measure of the depth of maintenance anesthesia, was longer for isoflurane than for sevoflurane. Furthermore, higher concentrations of both anesthetics suppressed the respiratory rate in degus. These new findings regarding inhalation anesthesia in degus will contribute to future developments in the fields of laboratory animals and veterinary medicine.

Laboratory rats, like mice, are a type of animal commonly used in scientific investigations as well as in basic aging and geriatric research. The selection of a rat strain is an important first step in the planning and design of an experiment due to physiological, anatomical, and ethological variations in each strain, which may significantly modify the expected results. In the present study, we characterized age-related changes, from 3 months old (mo) to 24 mo, in three male rat strains commonly used in medical research: RccHan^®️:WIST (RccHan:WIST), F344/NSlc (F344), and Slc:SD Rat (SD). The body weight, water/food consumption, and survival rate of each strain were physiologically evaluated. Hematological and biochemical values were analyzed every three months. Hematological results showed a decrease in lymphocytes and increases in other leukocytes from 12 mo in F344 and SD rats. The incidence of hematological disorder was 10-15% in F344 and SD rats from 18 mo. Increases in hepatic biochemical parameters (alanine transaminase (GPT/ALT) and aspartate transaminase (GOT/AST)) and cytopathological parameters (creatine phosphokinase (CPK)) were observed in male F344 rats at 12 mo. Triglycerides (TG) serum levels were significantly elevated in the 12 mo RccHan:WIST rats, while Lipase (LIP) levels were significantly reduced in 24 mo. The present results revealed significant variations in hematological and biochemical values in the different laboratory male rat strains due to genetic and nutritional-metabolic factors specific to each strain.