Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice.

The multimammate mouse (Mastomys natalensis; M. natalensis) has been identified as a major reservoir for multiple human pathogens including Lassa virus (LASV), Leishmania spp., Yersinia spp., and Borrelia spp. Although M. natalensis are related to well-characterized mouse and rat species commonly used in laboratory models, there is an absence of established assays and reagents to study the host immune responses of M. natalensis. As a result, there are major limitations to our understanding of immunopathology and mechanisms of immunological pathogen control in this increasingly important rodent species. In the current study, a large panel of commercially available rodent reagents were screened to identify their cross-reactivity with M. natalensis. Using these reagents, ex vivo assays were established and optimized to evaluate lymphocyte proliferation and cytokine production by M. natalensis lymphocytes. In contrast to C57BL/6J mice, lymphocytes from M. natalensis were relatively non-responsive to common stimuli such as phytohaemagglutinin P and lipopolysaccharide. However, they readily responded to concanavalin A stimulation as indicated by proliferation and cytokine production. In summary, we describe lymphoproliferative and cytokine assays demonstrating that the cellular immune responses in M. natalensis to commonly used mitogens differ from a laboratory-bred mouse strain.

Nephroblastoma in a Sprague Dawley rat unrelated to titanium dioxide nanoparticle exposure in utero.

Nephroblastoma is an embryonal tumour that has rarely been reported in laboratory rats. In this case report, a large nephroblastoma with peritoneal seeding was found during necropsy in an 11-month-old, female, Sprague Dawley rat. The rat had a history of indirect exposure to nano-TiO2 (titanium dioxide nanoparticles) during maternal gestation. A firm mass in the upper right abdominal quadrant was palpated. Four weeks later, the animal quickly declined. Nephroblastoma was confirmed by histopathology. Only one rat developed nephroblastoma among the ten littermates. Nephroblastomas in Sprague Dawley rats are typically spontaneous tumours with non-malignant mesenchymal elements. The capability to induce a nephroblastoma with nano-TiO2 is less likely in this case.

Selected Veterinary Concerns of Geriatric Rats, Mice, Hamsters, and Gerbils.

Improved husbandry and better knowledge of exotic pets have led to a gradual increase in the life span of pets, such as rats, mice, hamsters, and gerbils. Much of the information on these senior patients is derived from the laboratory animal studies and anecdotal practitioner information. Although the small size of some of the patients makes blood collection problematic for hematology and organ function testing, the advent of polymerase chain reaction testing and other molecular diagnostics is allowing practitioners to test for specific etiologies with the small biologic samples available. Radiology and ultrasonography also are valuable diagnostic modalities.

DISEASE AND PATHOLOGICAL CONDITIONS OF AN ENDANGERED RODENT, MICROTUS CALIFORNICUS SCIRPENSIS, IN A CAPTIVE-REARING FACILITY AND IN THE WILD.

Causes of morbidity and mortality and a survey of infectious disease agents were collated from wild and colony-raised endangered Amargosa voles (Microtus californicus scirpensis). Six voles from the wild and 295 voles in the captive-breeding colony were included in the study upon identification of an infectious agent during screening, identification of clinical signs of disease, or finding a pathological condition or infectious agent on necropsy. Findings included 28 significant or incidental pathological conditions of seven organ systems and 19 parasitic, viral, bacterial, or fungal agents. Several voles captured in the wild had fungal osteomyelitis of the tail that disseminated systemically in a vole brought from the wild to the colony and may have been caused by a Penicillium sp. Three voles reintroduced from the colony to the wild experienced inanition and subsequent severe hepatic and moderate renal tubular lipidosis. The most common significant pathological conditions in colony-reared voles were chronic interstitial nephritis with proteinosis; cardiomyopathy; trichobezoars that, in intestines or cecocolic junctions, sometimes induced local rupture or infarction with peritonitis; multifocal gastrointestinal ulceration and colibacillosis; acute renal tubular necrosis or nephritis; sepsis; hepatic and renal lipidosis; molar apical elongation sometimes progressing to invasion of the calvarium; and mammary tumors. Uncommon diagnoses included intervertebral disc disease; microvascular dysplasia; and multifocal bacterial abscessation. Common or clinically important infectious agents included Demodex sp. mites in hair follicles, Demodex sp. in esophageal mucosa, and an outbreak of tropical rat mites thought to have been introduced via the straw bedding; gastrointestinal Helicobacter sp.; attaching and effacing Escherichia coli; and Citrobacter braakii, a possible zoonotic bacterium. This survey of species-specific diseases and pathogens was possible because the established health surveillance program that is part of the species recovery plan allowed for monitoring of voles throughout the duration of their natural life spans in captivity.

Supernumerary Incisors in CB6F1 Mice Conditioned with Chemotherapy and Total Body Irradiation before Bone Marrow Transplantation.

Multiple adult female CB6F1 mice presented with supernumerary incisors after preconditioning with chemotherapy and total body irradiation for bone marrow transplantation (BMT). Mice received nonmyeloablative total body irradiation (3 Gy) and either cyclophosphamide or bendamustine, followed by BMT and posttransplantation cyclophosphamide or bendamustine. Here we describe the clinical presentation, µCT findings, and histopathologic evaluation of the affected mice. These analyses confirmed the gross diagnosis and revealed details of the abnormal tooth morphology. We surmise that the combination of total body irradiation and chemotherapy resulted in the abnormal formation of supernumerary incisors. Supernumerary teeth should be considered as a potential confounding factor in tracking weight loss after BMT. These conditions can be managed to allow animals to reach their intended scientific endpoint.

Review of gastric torsion in eight guinea pigs (Cavia porcellus).

The authors present eight cases of gastric dilatation and volvulus (GDV) in guinea pigs from the Department and Clinic of Exotic Animal and Wildlife Medicine, University of Veterinary Medicine, Budapest, Hungary between 2012 and 2016. Seven animals were operated on and two survived. Gastric torsion has been noted in many mammalian species. Gastric volvulus has a high morbidity and high mortality rate with a guarded to poor prognosis in all of these species. How GDV develops is still not widely understood. Postmortem examinations, in both our cases and previously reported cases, have failed to reveal the exact causes of the gastric torsions. The aetiology of gastric torsion in guinea pigs is probably multifactorial. Feeding fewer meals per day, eating rapidly, decreased food particle size, exercise, stress after a meal, competition, age, and an aggressive or fearful temperament, are all likely and potential risk factors for GDV development in a similar fashion to dogs. Sex, breeding, dental diseases, anatomical abnormalities, pain and pregnancy may also be contributing factors.

Pathological Findings in Wild Rats (Rattus rattus) Captured at Guafo Island, Northern Chilean Patagonia.

The black rat (Rattus rattus) is an invasive species and potential reservoir of significant pathogens of man, domestic animals and wildlife. During the 2012-2014 austral summers, 201 black rats were captured and examined on the uninhabited Guafo Island, in Northern Chilean Patagonia (43.593029°S, 74.713481°W). The mite Ornithonyssus bacoti caused lymphoplasmacytic and eosinophilic dermatitis in all infected rats (105/210, 52%), but no skin lesions were observed in rats infected with Nosopsyllus spp. and Plocopsylla spp. fleas. Eighty-eight rats (44%) had mild lymphoplasmacytic and eosinophilic enterocolitis and 61 of these rats were infected with the nematode Heterakis spumosa. In the liver, 63 animals (31%) had areas of necrosis with histiocytic and eosinophilic inflammation associated with multiple Calodium hepaticum eggs, and in 15 cases there was co-infection with several Taenia taeniaeformis strobilocerci. Mild interstitial lymphoplasmacytic sialadenitis with intranuclear inclusion bodies, suggesting cytomegalovirus infection, was observed in 28 rats (15%). In the lung, alveolar histiocytosis (69 rats, 34%) and perivascular lymphocytic infiltrates (46 rats, 23%) were the most common findings. There was mild to moderate lymphoplasmacytic interstitial nephritis in 52 rats (26%) and in 15% of these cases Leptospira spp. antigen was detected in the distal renal tubules. Some of the diseases of black rats on Guafo Island are likely to play a role in rat population dynamics. The endemic Guafo Island long-clawed mole mouse (Geoxus lafkenche), sea lions and fur seals may be at risk for infection by some of these rat pathogens.

Prevalence of Food Impaction-Induced Periodontitis in Conventionally Housed Marsh Rice Rats (Oryzomys palustris).

Marsh rice rats (Oryzomys palustris) fed a pelleted diet high in sucrose and casein have been used as a model for moderate to severe periodontitis. Here we characterize the prevalence, location, and histopathologic features of food-impaction lesions (FIL), a unique type of oral event, in rice rats fed standard pelleted rodent chow from weaning until 34 wk of age. Healthy female rats (n = 90; age, 4 wk) were weaned into groups (n = 10 to 24) and were euthanized at 4, 16, 22, 28, or 34 wk of age. At necropsy, high-resolution photographs of the 4 jaw quadrants were examined by 3 independent observers to determine the presence, number, and location of FIL. In addition, gross periodontitis was scored (scale, 0 to 4), and the hemimaxillar surface area containing FIL was measured. Serial sections of decalcified jaws were assessed histologically. The prevalence of FIL increased with age, and was 0% (baseline), 59.1%, 69.6%, 81.8% and 80.0% in rats at age 4, 16, 22, 28, and 34 wk, respectively. FIL were predominantly located (93.9%) in the maxillary palatal surfaces of the interproximal area between molars 2 and 3 and did not affect mandibular surfaces. The percentage of the hemimaxillar surface area occupied by FIL was 6.83%, 4.82%, 2.88%, and 6.52% in rats at age 16, 22, 28, and 34 wk, respectively. Histopathologic changes in FIL varied from localized gingivitis to larger, localized periodontitis-like lesions. These data indicate that FIL are common in rice rats fed standard rodent chow, are slight to mild in severity, and are localized to specific regions in the oral cavity, thus suggesting they may be a suitable model for local maxillary periodontitis when fed standard rodent chow.

Estrous Cycle Induces Peripheral Sensitization in Trigeminal Ganglion Neurons: An Animal Model of Menstrual Migraine.

BACKGROUND: Many women experience menstrual migraines that develop into recurrent migraine attacks during menstruation. In the human menstrual cycle, the estrogen level fluctuates according to changes in the follicular and luteal phases. The rat estrous cycle is used as an animal model to study the effects of estrogen fluctuation. OBJECTIVE: To investigate whether the estrous cycle is involved in migraine development by comparing the neuronal excitability of trigeminal ganglion (TG) neurons in each stage of the estrous cycle. MATERIAL AND METHOD: Female rats were divided into four experimental groups based on examinations of the cytologies of vaginal smears, and serum analyses of estrogen levels following each stage of the estrous cycle. The rats in each stage of the estrous cycle were anesthetized and their trigeminal ganglia were removed The collections of trigeminal ganglia were cultured for two to three hours, after which whole-cell patch clamp experiments were recorded to estimate the electrophysiological properties of the TG neurons. RESULTS: There were many vaginal epithelial cells and high estrogen levels in the proestrus and estrus stages of the estrous cycle. Electrophysiological studies revealed that the TG neurons in the proestrus and estrus stages exhibited significantly lower thresholds of stimulation, and significant increase in total spikes compared to the TG neurons that were collected in the diestrus stage. CONCLUSION: Our results revealed that high estrogen levels in the proestrus and estrus stages altered the thresholds, rheobases, and total spikes of the TG neurons. High estrogen levels in the estrous cycle induced an increase in neuronal excitability and the peripheral sensitization of TG neurons. These findings may provide an explanation for the correlation of estrogen fluctuations during the menstrual cycle with the pathogenesis of menstrual migraines.

Scratching Responses to Epidermal Injury in C57BL/6, DBA/2, BALB/c, and CD1 Mice.

Whereas early investigations into ulcerative dermatitis (UD) focused on the possibility of a primary dermatopathology, several recent studies have advocated scratching behavior as a primary driver for UD. The aim of this study was to assess whether B6 mice exhibit excessive scratching under resting conditions or when provoked by epidermal barrier disruption. We hypothesized that B6 mice would exhibit more spontaneous scratching behavior and that B6 mice would be more pruritic after mild epidermal barrier injury compared with the other strains and stock tested. The behavior of the retired breeder female C57BL/6J, DBA/2J, BALB/cByJ, and Crl:CD1 mice was videotaped for 60 min. Behavior filming occurred at 17:15 and at 07:00 the next morning prior to (baseline) and after tape-stripping to initiate epidermal barrier disruption. Scratching duration was recorded as brief (less than 3 s) or prolonged (3 s or longer), on the basis of observations during a pilot study. In contrast to the hypothesis, B6 mice did not scratch significantly more frequently, have more long-duration scratching events, nor have a higher median scratching duration of prolonged scratching as compared with the other types of mice tested. In fact, B6 mice showed the lowest average scratching frequency and duration under both conditions. B6 mice demonstrated increased scratching behavior after epidermal barrier disruption, but the increased scratching did not surpass the rate or duration of scratching in the other types of mice tested. These findings do not support the idea that a strain-related tendency toward exaggerated scratching behavior under resting or epidermal barrier disruption conditions predisposes B6 mice to UD.

Ulcerative Dermatitis in C57BL/6NCrl Mice on a Low-Fat or High-Fat Diet With or Without a Mineralized Red-Algae Supplement.

Ulcerative dermatitis (UD) is a spontaneous idiopathic disease that often affects C57BL/6 mice or mice on a C57BL/6 background. UD is characterized by intense pruritus and lesion formation, most commonly on the head or dorsal thorax. Self-trauma likely contributes to wound severity and delayed wound healing. Histologically, changes are nonspecific, consisting of ulceration with neutrophilic and mastocytic infiltration and epithelial hyperplasia and hyperkeratosis. Diet appears to have a profound effect on the development and progression of UD lesions. We investigated the incidence and severity of UD in C57BL/6NCrl mice on a high-fat western-style diet (HFWD) compared with a standard rodent chow. In addition, we examined the protective effects of dietary supplementation with a multimineral-rich product derived from marine red algae on UD in these 2 diet groups. HFWD-fed mice had an increased incidence of UD. In addition, mice on a HFWD had significantly more severe clinical and histologic lesions. Dietary mineral supplementation in mice on a HFWD decreased the histologic severity of lesions and reduced the incidence of UD in female mice in both diets. In conclusion, a high-fat western-style diet may potentiate UD in C57BL/6NCrl mice. Insufficient mineral supply and mineral imbalance may contribute to disease development. Mineral supplementation may be beneficial in the treatment of UD.

Elodontoma in Two Guinea Pigs.

Elodontoma was diagnosed in two pet guinea pigs, one involving a maxillary premolar tooth and the other affecting a mandibular incisor tooth. Diagnostic imaging, including radiographs, computed tomography, and oral endoscopy was performed in order to quantify dental disease. Diagnostic imaging was also used to guide treatment of acquired dental disease, which included intraoral restoration of normal occlusal plane and tooth extraction using an extraoral approach. These are the first histologically confirmed cases of elodontoma in guinea pigs.

Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

Spontaneous intraocular hemorrhage in rats during postnatal ocular development.

To study spontaneous intraocular hemorrhage in rats during postnatal ocular development and to elucidate the underlying mechanism, postnatal ocular development in the albino Wistar Hannover (WH) and Sprague-Dawley (SpD) and pigmented Long-Evans (LE) strains was analyzed. Pups (n = 2 to 5) from each strain were euthanized daily on postnatal days (PND) 0 through 21 and their eyes examined macroscopically and histologically; similar analyses were performed in 26 to 39 additional WH pups daily from PND 7 to 14. At necropsy, ring-shaped red regions and red spots were present in the eyes of WH and SpD rats. These lesions were attributed histologically to hemorrhage of the tunica vasculosa lentis or of the retina, choroid, and hyaloid artery, respectively. Similar intraocular hemorrhages occurred in LE rats, although the macroscopic alterations found in WH and SpD rats were not present in this strain. Among the 3 strains evaluated, the incidence of the intraocular hemorrhage was highest in WH rats. We here showed that intraocular hemorrhage occurs spontaneously during normal ocular development in rats regardless of the strain; however, the region, degree, and incidence of intraocular hemorrhage differ among strains. Hemorrhage in the tunica vasculosa lentis and hyaloid artery may result from the leakage of erythrocytes from the temporary vasculature of these tissues during regression. The mechanisms underlying hemorrhage in the retina and choroid remain unclear. To our knowledge, this report is the first to describe the spontaneous intraocular hemorrhage that occurs during postnatal ocular development in rats.

Electroencephalographic evaluation of decapitation of the anaesthetized rat.

The objective of this study was to evaluate the changes in electroencephalographic (EEG) power spectrum in response to decapitation of anaesthetized rats, in order to assess the nociception or otherwise of this procedure. Ten young adult male Sprague-Dawley rats were anaesthetized with halothane in oxygen and anaesthesia was maintained at a stable concentration of halothane between 1.20% and 1.25%. The rat's head and neck were placed through the opening of a small animal guillotine so that the blade of the guillotine was positioned over the atlanto-occipial joint of the rat's neck. The EEG was recorded in a five-electrode montage, bilaterally. After recording a 15 min baseline the rat was decapitated by swiftly pressing the guillotine blade and the EEG recording was continued until the signal was isoelectric on both channels. Changes in the median frequency (F50), 95% spectral edge frequency (F95) and total power of the EEG (Ptot) were used to investigate the effects of decapitation. During the first 15 s following decapitation, there were significant increases in the F50 and F95, and a decrease in the Ptot compared with baseline values. There was a clear window of time immediately following decapitation where changes in the EEG frequency spectrum were obvious; these changes in the EEG indices of nociception could be attributed as responses generated by the rat's cerebral cortex following decapitation.

Evaluation of a new side-stream, low dead space, end-tidal carbon dioxide monitoring system in rats.

The aim of this study was to evaluate a newly developed infrared side-stream capnograph with minimal sample volume for the continuous measurement of end-tidal carbon dioxide (CO2) concentrations in small rodents. Thirty-four male Wistar rats (weight 345 ± 70 g) were treated in accordance with the National Institutes of Health (NIH) guidelines for animal care. All experiments were performed with approval of the local animal care and use committee. Sepsis was induced by implanting an 18 gauge stent into the colon 24 h prior to the experiments, allowing a constant fecal leakage into the peritoneal cavity (25 septic and nine control animals). Hemodynamic variables and end-tidal CO2 were recorded continuously and arterial blood (5 × 120 µL) was sampled periodically for arterial blood gas analysis. After baseline controlled mechanical ventilation was randomized and titrated to either normocapnia (35-45 mmHg) or hypercapnia (65-75 mmHg) with exogenous application of CO2. A total of 155 paired CO2 measurements comparing end-tidal and arterial partial pressure were conducted. Side-stream capnography underestimated the CO2 partial pressure with a bias of -6.1 mmHg and a 95% limit of agreement from 6.7 to -19.1 mmHg. Our results suggest that side-stream end-tidal CO2 monitoring with a low dead space could be utilized in rats as a surrogate for the arterial CO2 measurement over a wide range of partial pressures in normal and septic animals.

A survey of rodent-borne pathogens carried by wild Rattus spp. in Northern Vietnam.

To examine the prevalence of human pathogens carried by rats in urban areas in Hanoi and Hai Phong, Vietnam, we live-trapped 100 rats in January 2011 and screened them for a panel of bacteria and viruses. Antibodies against Leptospira interrogans (22·0%), Seoul virus (14·0%) and rat hepatitis E virus (23·0%) were detected in rats, but antibodies against Yersinia pestis were not detected. Antibodies against L. interrogans and Seoul virus were found only in adult rats. In contrast, antibodies to rat hepatitis E virus were also found in juvenile and sub-adult rats, indicating that the transmission mode of rat hepatitis E virus is different from that of L. interrogans and Seoul virus. Moreover, phylogenetic analyses of the S and M segments of Seoul viruses found in Rattus norvegicus showed that Seoul viruses from Hai Phong and Hanoi formed different clades. Human exposure to these pathogens has become a significant public health concern.

Occurrence of pathogens in wild rodents caught on Swedish pig and chicken farms.

A total of 207 wild rodents were caught on nine pig farms, five chicken farms and five non-farm locations in Sweden and surveyed for a selection of bacteria, parasites and viruses. Lawsonia intracellularia and pathogenic Yersinia enterocolitica were only detected in rodents on pig farms (9% and 8% prevalence, respectively) which indicate that these agents are more likely to be transmitted to rodents from pigs or the environment on infected farms. Brachyspira hyodysenteriae (1%), Brachyspira intermedia (2%), Campylobacter jejuni (4%), Campylobacter upsaliensis (2%), leptospires (7%) and encephalomyocarditis virus (9%) were also detected from rodents not in contact with farm animals. Giardia and Cryptosporidium spp. were common, although no zoonotic types were verified, and Salmonella enterica was isolated from 1/11 mice on one farm but not detected by PCR from any of the rodents. Trichinella spp. and Toxoplasma gondii were not detected.