Male BALB/c mice isolated after weaning were housed two mice per cage at the age of 10 weeks. After 1 week, each pair of mice was observed for social dominance, and compared with control mice kept in isolation. The Preputial gland in the socially dominant animal was histologically examined. The preputial gland consisted of a congregation of branched simple tubuloacinar gland and typical holocrine secretion on morphological examination. Acinar cells in the dominant animals were large, multiplicative and hypertrophic compared with those of controls and subordinates. Dominant animals required copious secretion for attainment and maintenance of a dominant social position. Acinar cells of subordinates were very small, flattened and atrophied because fatty secretion particles filled the luminal duct. These accumulated secretion particles pressed the acinar cells and caused degeneration. Not only luminal acinar cells but also central acinar cells and some basal acinar cells were degenerated. Electron micrographs showed that basal acinar cells in dominant animals contained many mitochondria, agranular endoplasmic reticulum and free ribosomes in the cytoplasm, whereas those of subordinates contained myelin bodies and lipid droplets. Therefore, it is suggested that the synthesis of secretion particles in acinar cells of subordinates hardly occurred.
Male rats of the WBN/Kob strain, which are known to spontaneously develop diabetes with aging, were examined for histopathological changes in the retina. Five rats (10 eyes) each of WBN/Kob and Wistar/ST as a control were used, and the thickness of the retinal layers, both the central region and the peripheral region of the retina, were measured on weeks 1, 2, 3, 5, 9, 13, 17, 23, 27, 36, 45, 54, 67 and 80 after birth. The rod and cone cell layer in WBN/Kob rats was under-grown, and its thickness decreased 71.7% in the central zone and 59.3% in the peripheral zone of the retina compared with that of the control. In the central and peripheral retina, the rod and cone cell layer, outer nuclear layer and outer plexiform layer, as well as the inner plexiform layer in the central retina, gradually decreased in thickness from 5-45 weeks of age. In the central and peripheral parts of the retina, the number of nuclei decreased in accordance with the thinning of the nuclear layer. The thinned layers showed only cell loss. The rod and cone cell layer of the peripheral retina was thinner than that of the central retina. We obtained the following findings in the retina of male WBN/Kob rats. First, the rod and cone cell layer is undergrown compared with that of the control. Second, the first change occurred in the rod and cone cell layer. Third, the thinning of the rod and cone cell layer appeared at 5 weeks of age, and thinning with aging was slow. And finally, the thinning of the peripheral retina was more severe than that of the central retina. From the above findings, it seems that retinal changes in WBN/ Kob rats are similar to the retinal degeneration of rds mice (retinal degeneration slow mice) and that WBN/Kob rats provide a useful animal model for human retinopathy.
The development of the musk gland in house musk shrews aged 0 to 21 days was studied lectin histochemically. On about 3 days of age, the musk gland could be discriminated from surrounding skin. This organ developed markedly on days 3 to 7, and its development continued to 21 days of age. Histologically, on day 1, the bulges that should develop into musk glands were identified in the vicinity of hair germs. On days 3 to 7, these bulges developed markedly, and on day 21 their structure revealed almost the same morphology with that in mature musk glands. We used 7 lectins; ConA, RCA I, PNA, SBA, UEA-I, DBA, and WGA. On day 1, 6 lectins except for WGA labelled the cell of the musk gland. WGA began to label it on day 3. Until 7 days of age, lectins bound to only the cytoplasm of the cell of musk glands. On days 12, . however, PNA and UEA-I labelled the cell membrane equally, and RCA I labeled it on day 21.
Age-related changes of 27 items in serum chemistry were investigated in Sprague-Dawley rats of both sexes from 6 to 30 weeks of age. The following 12 items were shown as an increase in those values during growth and maturity, i.e., total protein, albumin (female only), glucose, total cholesterol, triglyceride, phospholipid (female only), β-lipoprotein, cholinesterase (female only), asparate aminotransferase (female only), creatinine, direct-bilirubin and total-bilirubin. However, the following 4 items decreased with aging, i.e., asparate aminotransferase, alkaline phosphatase, creative phosphokinase and inorganic phosphorus. No age-related changes were found in the values for calcium, sodium and chloride in both sexes and for alanine aminotransferase, cholinesterase and albumin in males. The sex differences were shown in the following 12 items: higher values in males were alkaline phosphatase, creatinephosphokinase, glucose and inorganic phosphorus, and higher values in females were cholinesterase, albumin, phospholipid, non-esterified fatty acid, urea nitrogen, direct-bilirubin, total-bilirubin and serum iron. No sex-related differences were found in the values for calcium, sodium, chloride and total cholesterol.
To define the developmental fate of two different stages of embryos existing together in the mouse reproductive tract, different stages of fresh and frozen-thawed embryos were transferred separately into the oviducts of identical recipients. ICR and FvB embryos were flushed from the oviducts and/or uterus of superovulated females on Day 1 (2-4-cell stage) and Day 2 (8-cellmorula stage) of pregnancy. Day 1 embryos were transferred separately to the right or left oviduct of recipients, while the other oviduct received Day 2 embryos. There were no significant differences between Day 1 and Day 2 embryos with respect to the number of implantation sites and live fetuses in either the fresh or frozen-thawed embryos. These results concerning to the embryonic stage were similar to those of control experiments, in which Day 1 or Day 2 embryos were transferred to both right and left oviducts of recipients. Furthermore, no strain differences were observed in this study. No developmental retardation or anomalies were observed in fetuses derived from either Day 1 or Day 2 embryos. The embryo transfer in this study revealed that differences in developmental stage at preimplantation were synchronized by the maternal uterine environment.
Osteopetrosis is an inherited metabolic disease which produces an excessive accumulation of bone caused by deficiency of osteoclasts. It is characterized by systemic bone sclerosis, cranial deformation and failure of tooth eruption due to defective bone resorption. In this study, morphological change of the mandible was observed in growing Osteopetrotic (op/op) mutant mice. Deformation of the condylar process, non-ossification of the condyle head and underdevelopment of the lateral pterygoid muscle were observed in the mutant mice. Although these phenomena were brought about by failure of the bone remodeling, it was simultaneously suggested that the ossification of the condyle head concerned with the mastication.
To clarify the pathogenesis of vulnerability to acute gastric mucosal lesion (AGML) in diabetes mellitus (DM), we investigated histopathologically the gastric mucosa of the fundic gland in streptozotocin-induced DM rats. The length of the mucosa and the thickness of the surface epithelial cell (SEC) layer were measured, and the number of proliferating cell nuclear antigen (PCNA) positive cells was counted. As results, compared with control rats, the ratio of the length of SEC layer to that of mucosa, and the number of PCNA positive cells were significantly decreased in DM rats, whereas the length of the mucosa tended to extend in DM rats. Consequently, it is considered that attenuation of mucosal barrier in the SEC layer can be closely associated with susceptibility to occurrence of AGML in DM.
The relationship between behavioral change and hippocampal lesion was studied in ddY male mice, at 4.5, 20, 40 and 60 weeks of age. In passive avoidance response, the aging mice (40 and 60 weeks of age) showed shorter latency than young mice (4.5 weeks of age) . The degenerated pyramidal cells were more numerous after 40 weeks of age in the CA3 than CA1. The mean incidence of the degenerated pyramidal cells in the CA3 was 20.8% at 60 weeks of age. In 71.9% of mice, impairment of passive avoidance response was associated well with hippocampal lesions. These results indicate that the hippocampas plays some role in the memory in mice. The ddY mice may be possible to use as models for reversible hippocampal lesion.
There is little information about microenvironments within laboratory animal cages, although several guidelines on the macroenvironment in laboratory animal rooms have been reported. We have developed a forced-air ventilation system (FVMIS) to improve laboratory animal wellbeing. In this study, we tested the performance of the FVMIS in terms of temperature and ammonia concentration within cages. Continuous measurement of temperature and ammonia concentration was carried out in FVMIS cages housing 5 rats each. The average temperature within the cages was 22°C to 24°C, and the temperature difference among cages was 0.93°C. The air exchange rate used was 65 changes per hour. FVMIS was capable of controling the temperature within cages uniformly and accurately with a lower air exchange rate than with the conventional system. The ammonia concentration reached 20 ppm within 9 days in a filtercapped conventional cage, but took 13 to 16 days to reach 20 ppm with FVMIS. It appears that FVMIS is capable of suppressing the ammonia concentration increase in cages, thereby reducing the frequency of cage changes and the stress to laboratory animals when cages are changed. In the present study, it was confirmed that FVMIS contributes not only to microenvironmental control in terms of temperature and ammonia concentration with a lower air exchange rate, but also to animal wellbeing.
The incidence and morphological characteristics of senile plaque and amyloid angiopathy in the cerebrum of six aged cynomolgus monkeys (Macaca fascicularis), 20 to 29 years old, were studied histopathologically and irnmunohistochemically. By periodic acid methenamine silver stain (PAM) and alkaline Congo red stain, senile plaques were detected in 5 out of 6 cases, and 3 of them were positive for amyloid in the wall of capillaries and arterioles in the cerebral cortex. Senile plaques were classified into three types. Mature plaques, including classical and primitive types, were more frequently observed than the immature diffuse type. Senile plaques were often seen in the cortex of temporal lobe, putamen and head of caudate nucleus. Since mature types of senile plaques were seen frequently around vascular amyloid deposition and no amyloid angiopathy was detected in the areas without senile plaques, the close relation between senile plaque of the mature type and amyloid angiopathy might be considered. All senile plaques and amyloid angiopathy were positively stained immunohistochemically with antibody against amyloid β-protein (AβP) 1-40 synthetic peptide, but all diffuse and some primitive plaques were negative for antibody against AβP 8-17 synthetic peptide. Neither senile plaque nor amyloid angiopathy was detected in the cerebrum of 15 young monkeys, 9 to 11 years old, examined as controls.
The present study was conducted to analyze biochemical marker genes and to clarify genetic variation in 4 Mongolian gerbil (Meriones unguiculatus) strains (MGS/Sea, MON/Jms Gbs, Kwl: Mongolian Gerbil and Hos: Mongolian gerbil) maintained in Japan. Cellulose acetate, starch gel or agar gel electrophoresis was used. Of the 23 kinds of proteins detected, variation was found only in liver acid phosphatase (Acp2) ; no variation in other proteins was found within or among strains. The results suggest that these 4 Mongolian gerbil strains are genetically similar. A strain difference was found in theAcp2locus of liver acid phosphatase. The Kwl: Mongolian Gerbil strain had a band ofAcp2locus, whereas MGS/Sea, MON/Jms and Hos: Mongoian gerbil strains did not.
One-way mixed lymphocyte reaction (MLR) tests were carried out on three strains of Korean native goat, A, D and E, which had been fixed by DRB/DQB haplotype in the major histocompatibility complex (MHC) class II region. In the case of MLR combined within the same strain, the values for the stimulation index (S.I.) were from 1.08±1.26 (within the D strain) to 3.19±2.28 (within the A strain) . On the other hand, in the case of MLR combined for the different strains, the S.I. values were from 10.47±4.31 (E strain as the stimulator and A strain as the responder) to 36.08±7.42 (D strain as the stimulator and E strain as the responder) . The difference between the S.I, values for the same and different strains was clearly significant (p<0.001) . To elucidate the effect of a combination of the DRB/DQB haplotype on the S.I. values, A and E strain and AE heterozygote animals were used in the MLR tests. With MLR combined heterozygote as the stimulater and homozygote as the responder (A or E strain), the mean S.I. value was 9.62±3.9. This value showed high levels in the different strains, but showed a significant difference from that of the same strain (p<0.001) . On the other hand, with MLR combined homozygote as the responder (A or E strain) and a heterozygote as the stimulater, the mean S.I. value was 1.46±1.17. This value showed low levels as well as within the same strain, but showed a significant difference from that of different strains (P<0.001) . These results indicated that the responses in the MLR tests were associated with the DRB/DQB haplotypes. This suggested that at least both MHC class II DR and DQ antigens of goats were related to the immune-responses equivalent to the human MHC (HLA) class II antigens. Moreover, we concluded that Korean native goat strains fixed for DRB/DQB haplotype possessed an effective genetic background as a large experimental animal for organ transplant studies.
In order to utilize Syrian hamsters in selection experiments, we investigated desirable conditions of feed and mating age for reproduction in females. Hamsters were subdivided into two groups, raised on pellet feed for herbivores (ZC-2) and breeding (MB-1), respectively. Half of the hamsters in each group were switched to the other feed, respectively, after mating. They were mated at S or 12 weeks of age. In the group that has been fed on ZC-2 before mating and MB-1 after mating, there was significantly more females giving birth and weaning, and exhibited the largest litter size and litter weight at 3 weeks of age (P<0.01) . The hamsters of the groups mated at 12 weeks of age exhibited a higher percentage of females giving birth and litter size and litter weight at birth than those at 8 weeks of age, but that was no significant difference in litter size and litter weight at 3 weeks of age. We conclude that Syrian hamsters raised by fibrous feed before mating gave optimal reproductive performance.
Urinalysis, hematological and blood chemical examinations and measurement of organ weights were carried out for the purpose of collecting background data on Weiser-Maples (WM) which was established as an inbred strain of guinea pigs. The results were compared with those for the commercial guinea pigs, Std: Hartley (H) . In addition, the measurement methods for urinary specific gravity and whether centrifugation of urine influences the results of urinalysis or not were examined. The specific gravity values calculated from the volume and weight of urine were highly correlated with those from the refraction rate. The results of urinalysis of the supernatant of centrifuged urine were similar to those of urine not centrifuged, but the results suggested that the use of the supernatant provided a more accurate measurement of urine in guinea pigs. The positive rate for urinary protein was higher in the WM strain (38.9%) than in the H strain (0%) . Although the WM strain showed higher or lower values than the H strain in some items of hematological and blood chemical examinations and organ weights, we could not regard them as characteristic of the WM strain.
We have a big problem with the abuse of amphetamine and its close relative, methamphetamine (MAP) in Japan. As an animal model of people who abuse MAP, male and female rats were treated with MAP (0.1-10.0 mg/kg/day) for a long time. The results obtained in the present study were as follows. 1. Body weights in MAP-treated groups showed a dose-dependent decrease with loss of food intake. 2. Food intake in rats treated with MAP decreased, compared with the control, but when treatment with MAP was discontinued, food intake increased dramatically. 3. In a blood biochemistry assay, the turnover of protein and lipid was suppressed in rats after MAP. 4. The administration of MAP appeared to disturb the estrous cycle in female rats.
The post mortem examination of 158 Mongolian gerbils (80 males and 78 females) revealed that 61 cases (38.6%) of them carried spontaneous neoplasms [22/80 (27.5%) of males and 39/78 (50%) of females] . In the male, sebaceous gland carcinoma at the abdominal skin was observed in 18/22 (81.8%) of tumor cases. In the female, granulosa cell tumor was seen in 31/39 (79.4%) of tumor cases. These two tumor types were markedly predominant in gerbils older than 3 years. The each incidence of other types of tumor was less than 5% in male and female animals.
Pulmonary metastases of chinese hamster mesenchymal chondrosarcoma cell lines, MCS-1 (undifferentiated type) and MCS-8 (differentiated type), were examined by intravenous transplantation into athymic nude mice. The incidence of pulmonary metastasis of MCS-1 was 100% and that of MCS-8 was 33% at the 23rd day after transfer. Mean number of metastatic nodules in the lung was 41 in the former and only 3 in the latter. Mean survival time of mice with MCS-1 injection (5×104 cells) was 27 days and that with MCS-8 (5×104 cells) was 48 days after transfer. At the 42nd day after transfer of MCS-8, however, the incidence of pulmonary metastasis was 100%. These data suggest that the tumor growth rate in the metastatic lesion, as well as the affinity to the target organ, is very important for evaluation of experimental metastasis.
The open-field test was carried out on NOD mice of both sexes between the ages of 40 to 300 days. The behavior of both sexes of mouse was observed for 3-minute periods with an interval of 20 days. The mean scores of ambulation and rearing increased at the ages of 40-80 days old, and both scores decreased more than 100 days old. The onset of overt diabetes (DM) in female mice were observed after 120 days old. After the onset of DM with great loss of body weight, the scores of ambulation and rearing were dramatically decreased. Other parameters, urination, defecation, and preening were not changed with age of both sexes. These data suggest that conspicuous weight loss with the expression of overt diabetes in NOD female mouse might correlate to decrease of the ambulation and rearing scores.
Protrusion of hyperplastic upper molar teeth (macrodonts) into the cranial cavity was observed in the Japanese field vole. Protrusions of the upper molars occurred on both sides, but were large on the left than on the right. The teeth invaded the cranial cavity and brain parenchyma. Large concavities on the ventral side of the brain were interposed between the lateral olfactory tract and the optic tract. Invation by one macrodont reached the basal nuclei, hypothalamic and thalamic nuclei. The brain was deformed bilaterally, and nearly the entire olfactory bulb, globus pallidus, internal capusule, and lateral preoptic nucleus, and a portion of the hypothalamus, thalamus and anterior commissure were absent on the left side.
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