Brown Norway (BN) rats have been found to develop granulomatous pneumonia with high spontaneous incidence under normal husbandry conditions. In our laboratory, ambient particles from the animal housing environment were suspected to be involved in the pathogenesis of these pulmonary lesions. In the present study, we correlated the histopathology of spontaneous granulomatous pneumonia with the cytology of bronchoalveolar lavage fluid (BALF) analysis and animal room particle counts. The results show that the sum of the macroscopic lesion score in the lung correlated with the number of eosinophils in the BALF. Microscopically, the severity of granulomatous lesions was significantly correlated with both pulmonary eosinophils and the number of eosinophils in the BALF, but not with those of neutrophils or lymphocytes. In addition, the histological features of the lesions were not influenced by housing conditions or sensitization with ovalbumin. Ambient particles (0.3-1.0 μm in diameter) in the animal room environment were measured and compared with the number of eosinophils in BALF. Interestingly, there was a significant correlation between them, suggesting a possible relationship between environmental particles and the pathogenesis of granulomatous pneumonia in BN rats. However, further study is needed to clarify the pathogenic mechanism.
Chicken inbred lines of the GSP, GSN/1, PNP/DO and BM-C have been established by selection of a specific allele at the B blood group locus (MHC B-G region) and other polymorphic loci through pedigree mating. To extend the potential of these inbred lines as experimental animals in Aves, we assessed the antigenic homogeneities of the MHC antigens by three immunological methods. Antigenic variations of red blood cells (RBCs) were surveyed in the inbred lines and a random-bred line (NG) derived from the Nagoya breed by using ten kinds of intact antisera produced in the inbred line of chickens against RBCs of a red junglefowl and hybrids. In the hemagglutination test, no individual variations were found within the inbred line at all, while all the ten antisera detected highly heterogeneous reactions in individuals of the NG. The reciprocal one-way mixed lymphocyte reactions gave constantly higher stimulation responses (P<0.01) between individual pairs from the inbred lines having different B alleles compared to pairs within the inbred line, while lower stimulation was observed between pairs of the GSP and GSN/1 inbred lines both having the B21 allele. In reciprocal skin transplantation, the transplanted skingrafts within the inbred line and between individuals from the GSP and GSN/1 inbred lines survived more than 100 days, while all the skingrafts showed signs of rejection within 7 days among the inbred lines having different B alleles. The results obtained by the three practical methods coincidentally indicated that the individuals in the respective four inbred lines were histocompatible, and further, that the GSP and GSN/1 individuals were histocompatible.
Sepsis is characterized by various symptoms, signs and underlying pathophysiology. To investigate possible mechanisms underlying this diversity, we compared the cardiovascular effects of lipopolysaccharide (LPS) derived from Escherichia coli (E-LPS) with those of LPS from Pseudomonas aeruginosa (P-LPS) in rats. We also examined the possible roles of tumor necrosis factor-α (TNF-α) and oxidative stress in LPS-induced cardiovascular damage. E-LPS (10 mg/kg body weight) or P-LPS (2 mg/kg body weight) was administered intravenously to Wistar rats. Echocardiography was serially performed. E-LPS induced an increase in left ventricular fractional shortening that persisted for at least 6 h, whereas P-LPS elicited an initial increase and a subsequent decrease in this parameter. Histological analysis revealed that P-LPS induced interstitial edema, congestion, intramyocardial bleeding, myocardial necrosis, infiltration of inflammatory cells, and formation of fibrin thrombi in the heart, whereas no pathological changes were apparent in the hearts of rats treated with E-LPS. Furthermore, the plasma concentration of TNF-α in rats treated with P-LPS was greater than that in rats treated with E-LPS, but the glutathione redox ratio in the heart was not affected by either type of LPS. In conclusion, E-LPS and P-LPS induced distinct patterns of functional and structural responses in the cardiovascular systems of rats. These differential responses may be attributable in part to the difference in the associated increases in the plasma concentration of TNF-α. The cardiovascular effects of LPS thus depend on the causative organisms.
In this study we assessed the effectiveness of fluid viscosities placed in the peritoneal cavity to prevent postoperative peritoneal adhesions. Thirty-six Wistar albino female rats (average weight: 160 ± 30 g, average age: 6.5 months) were divided into three groups of equal number. A standard adhesion pattern was formed in each group. Then, 3 ml isotonic sodium chloride solution (relative viscosity value: 1) was added into the peritoneal cavity of group 1; 3 ml standard 6% hydroxy ethyl starch solution (HES) (relative viscosity value: 2.9) was added into the peritoneal cavity of group 2; and a standard HES solution that was concentrated by dehydration (relative viscosity value: 249.7) was added into the peritoneal cavity of group 3. All rats were sacrificed on postoperative day 10 and the adhesions that formed were graded. In group 1, grade-3 adhesions developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. In group 2, grade-3 adhesions developed in 1 (8.3%) rat, grade-2 developed in 6 (50%) rats, and grade-1 developed in 5 (41.6%) rats; in group 3, grade-3 adhesions developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. The adhesion scores of group 3 and group 1 were equal to each other (P=1), while the adhesion score of group 2 was significantly less (χ2:18.23, P<0.001). Increasing the viscosity of fluids that are inserted in the peritoneal cavity may reduce the formation of postoperative peritoneal adhesions till a critical value of unknown viscosity is achieved. The mechanism behind this process remains unclear.
The spontaneously diabetic Torii (SDT) rat has recently been established as an animal model of non-obese type 2 diabetes, in which ocular complications severe occur. However, the function and morphological features of the diabetic renal lesions in SDT rats have not been reported in detail. Therefore, we evaluated changes over time in renal lesions in SDT rats. In addition, SDT rats were treated with insulin to observe whether these renal complications are caused by hyperglycemia. Renal functional parameters and renal lesions were monitored in SDT rats from 8 to 68 weeks of age. Sprague-Dawley (SD) rats of similar age were used as control animals. In the insulin-treated group of SDT rats, insulin pellets were implanted at 24 weeks of age to compare the development of renal lesions. The SDT rats began to develop hyperglycemia at 20 weeks of age. In the histopathological examination of the kidney, glycogen deposition of the renal tubular epithelium and renal tubular dilation were observed from 24 weeks of age in the untreated SDT rats, and the changes in the renal tubules markedly progressed with aging. Moreover, thickening of the glomerular basement membrane was observed from 32 weeks of age. At 50 weeks of age, the glomeruli showed increase of mesangial matrix, with predominantly diffuse lesions showing by 68 weeks of age. The mesangial proliferation gradually progressed. In the SD rats, no renal lesions were present at 50 and 68 weeks of age. SDT rats with insulin treatment remained normoglycemic throughout observation and their renal functional parameters were normal. Glycemic control in SDT rats prevented the development of renal lesions. The features of SDT rats indicate their usefulness as an animal model for investigating diabetic nephropathy.
Bedding and nesting materials can improve the health and environmental welfare of laboratory mice. This study was carried out to examine which items are actually preferred by mice. Two series of studies were performed on four types of floor-covering materials (Wood-shavings (Clean-chipTM), Cloth (AgrebeTM), Recycled-paper (Paper-cleanTM), Paper (Care-feeazTM)), and on four types of nesting materials (Recycled-paper (Shepherd-shackTM), Cloth (AgrebeTM), Wood (Wood-cylinder), and Polycarbonate (Mouse-iglooTM)). Preference of bedding materials was judged by the time length of staying in a cage. The results indicate that mice stayed in the cloth material (AgrebeTM) longer than in other bedding materials (light 51.1 ± 5.3%, dark 51.5 ± 2.6%). In the second experiment, the duration of stay in AgrebeTM was significantly longer than that in the other nesting materials in the light phase (70.9 ± 2.4%). In the dark phase, staying time both in AgrebeTM and Shepherd-shackTM were significantly longer. These data suggest that cloth bedding and nesting is recommended for the environmental enrichment of laboratory mice.
Skin morphology of the Clawn miniature pig (CMP) was investigated at the axilla, medial thigh, back and loin. The mean thickness of the epidermis (excluding the corneal layer), the mean number of layers of keratinocytes comprising the epidermis and the mean height of keratinocytes were assessed morphometrically. When observed under a light microscope, the skin of the CMP resembled human skin. Morphometrically, skin from the back and loin of the CMP most resembles human skin. Electron microscopic observations revealed sparse but typical Birbeck granules in the epidermal Langerhans cells of the CMP. The results of the present study indicate that CMP skin is potentially useful as a model for human skin.
The characteristics and gender differences of the pulmonary hemodynamic parameters of 16 Clawn miniature pigs were examined and the data were compared with reports concerning dogs and other pig species. The pulmonary systolic, diastolic and mean arterial blood pressures of the mini-pig were slightly higher than those of the dog, respectively, but both the right atrial pressure and pulmonary capillary wedge pressure were within the normal physiological ranges of the dog. Concerning gender differences in hemodynamic parameters of the mini-pig, the female values, except the right atrial pressure, were slightly higher than those of the male, but no significant differences were recognized. The present study results will help pulmonary researchers understand the differences between Clawn miniature pigs and dogs for accurate analysis of experimental results.
The ground squirrel is used as an experimental animal because of its unique biological nature. A 3-year-old female Richardson's ground squirrel developed a mass, 1.5 cm in diameter, in the buccal mucosa. The mass consisted of neoplastic epithelial cells showing acinar, ductular, intraductal papillary, solid, and lobular growth patterns; the cells were immunoreactive to cytokeratin, cyclooxygenase-2 (a marker of malignancy) and TGF-β1. After resection, the tumor recurred with increased area having a solid or lobular pattern with little differentiation. This tumor was diagnosed as an adenocarcinoma arising from the buccal gland, the first case reported in the ground squirrel. A prominent desmoplastic reaction was present. The interstitial cells reacted to α-smooth muscle actin and vimentin, indicating a myofibroblastic nature, presumably induced by epithelial TGF-β1.
The DBA/2J mouse strain is a standard laboratory strain that is widely used for biomedical research. This strain, however, suffers from poor reproductive performance. In addition, the conditions for reliable embryo transfer (ET) of this strain have not been elucidated. The intention of this study was to determine the optimal number of embryos for transfer that allow the effective production of DBA/2J offspring. In the experiment, 7 to 15 embryos per oviduct were transferred into pseudopregnant ICR females. A relatively high success rate for pup production was observed when a large number of DBA/2J embryos (30 embryos per female) were transferred. This result shows that the ET efficiency of the DBA/2J strain can be improved by increasing the number of transferred embryos.
The joggle mouse is a recessive ataxic mutant carrying an unknown mutation in a C3H/He (C3H)-derived chromosomal segment. Taking advantage of the mouse genome database, we selected 127 DNA microsatellite markers showing heterozygosity between C3H and C57BL/6J (B6) and a first round of screening for the joggle mutation was performed on B6-jog/+ partial congenic mice (N4). We identified 4 chromosomal regions in which 13 microsatellite markers show heterozygosity between C3H and B6. Then, we analyzed the genotype of these 4 chromosomal regions in mice that showed the joggle phenotype and mapped the jog locus between markers D6Mit104 (111.4 Mb) and D6Mit336 (125.1 Mb) (an interval of 13.7 Mb) on chromosome 6. By using a partial congenic strain together with the mouse genome database, we successfully mapped the chromosomal localization of the jog locus much more efficiently than by conventional linkage analysis.
To assess delayed fertility in male growth-retarded (grt) mice with congenital primary hypothyroidism, their testes were chronologically examined. The testicular weight in grt mice was significantly lower than age-matched normal mice until 8 weeks but was comparable at 13 and 26 weeks. While normal mice had mature sperm cells in both testes and epididymides at 5 weeks, age-matched grt mice did not. The size of the seminiferous tubules in testes of grt mice was smaller than that of normal mice before 13 weeks but was comparable at 26 weeks. These findings suggest that male grt mice might need more than 13 weeks to develop mature testes.