This study found that the thymus of hea/hea mutant mice (hea mice) became atrophic in early phase of life and that the differentiation of CD4-CD8- (Double Negative; DN) into CD4+CD8+ (Double Positive; DP) cells during the development of T cells in the thymus was abnormal. The thymus development of hea mice was different from that of normal littermates. After 6 days of age, the numbers of thymocytes in hea mice decreased. The total numbers of DP cells in the thymus of hea mice reached the maximum at 6-9 days of age and then decreased after 10 days. The total numbers of DN cells in the thymus were almost constant in hea mice and normal littermates. These results indicate abnormalities in the process of differentiation from DN to DP cells in the thymus of hea mice. Flow cytometoric analysis indicated the presence of a large number of apoptotic and necrotic cells in the thymus of 13-15-day-old hea mice. However, there were no significant differences in the amount of mRNAs of Fas, Fas ligand and IL-7 between hea mice and normal littermates. Splenocytes from hea mice produced the same amount of cytokine mRNAs as normal littermate mice and the hea mutation (Ttc7(fsn-hea)) did not affect serum levels of IgM immunoglobulin. However, activated T cells from hea mice showed more secretion of cytokines derived from Th2 cells than from Th1 cells, so they might be affected by abnormalities of the immune system.
Laboratory mice were divided into 2 groups and introduced to different rooms immediately after being transferred from a mouse farm. Polymerase chain reaction followed by denaturing gradient gel electrophoresis were performed on the V6-V8 regions of bacterial 16S rDNA obtained from fecal samples at 0, 1, 2, 3, 4 and 8 weeks after the introduction. Binary data were obtained from banding patterns, and Euclidean distances for each week were calculated and analyzed by cluster analysis and non-metric multidimensional scaling. Euclidean distances were significantly higher at weeks 1 and 2 than at week 0 in both groups, although the distances between the 2 groups were significantly higher after week 1 than week 0. The distances between the 2 groups were significantly higher than those within each group at weeks 4 and 8. Mice in the 2 groups formed clusters at weeks 2 and 3 respectively, and mice were divided into 2 clusters by their respective groups at weeks 4 and 8. Mice in the 2 groups were distributed on opposite sides of the origin on the 2-dimensional plane after week 2. These results suggest that mouse fecal flora changed characteristically, according to the local environment after introduction.
This study was done to assess the effects of Urtica dioica, Plantago major and Hypericum perforatum L herbal mixture in the MCIA rat model. In addition, a new pathological and clinical arthritis lesion assessment was developed. Sprague-Dawley (SD) rats were immunized with bovine type II collagen and muramyl dipeptide (MDP). Commercial herbal extracts were administered daily to the rats after the immunization for the course of experiment (90 days). Rats were boosted with a second collagen-MDP emulsion 60 days after the first immunization. Paws were daily evaluated macroscopically for redness, swelling, distortion, or ankylosis of the joints. On the day of sacrifice, rat paws were assessed for histopathologic changes. Herbal mixture administration decreased the clinical lesion manifestation in the MCIA rat model and led to development of similar or slightly more severe histopathological lesions compared to rats that did not receive the treatment. The clinical arthritis signs appeared as early as 13 days after the first MDP/collagen injection and with peak incidence at 20 days post-immunization. Histopathologically, animals showed changes ranging from mild to very severe. Administration of the herbal mixture used in this study had a clinical therapeutic effect on the course of the clinical manifestations in the MCIA model, but the herbal treatment had no such effect on the histopathological lesion development and even led to slightly more severe lesions. Rats in the MCIA model developed prominent clinical and histopathological changes that were comparable to rheumatoid arthritis (RA) lesions in humans.
The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. The SDT-fa/fa (SDT fatty) rat shows overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with the SDT-+/+ (SDT normal) rat. However, the features of the diabetic complications in the SDT fatty rat have not been reported. In the present study, the incidence and the progression of diabetic complications in the SDT fatty rat were examined, and compared with those of the SDT normal rat. Renal function parameters, such as blood urea nitrogen, urine volume and urinary protein, increased from 4 weeks of age in the SDT fatty rat, and pathological findings in the renal tubule were observed from 8 weeks. Furthermore, cataract was observed in the SDT fatty rat from 8 weeks of age, and prolongation of peak latencies on electroretinograms was observed at 16 and 24 weeks of age. On the other hand, in the SDT normal rat, renal or ocular changes were observed from 24 weeks of age. With early incidence of diabetes mellitus, diabetes-associated complications in the SDT fatty rat were seen at younger ages than those in the SDT normal rat. In conclusion, the SDT fatty rat is expected to be a useful model for the analysis of diabetic complications and the evaluation of drugs related to metabolic diseases.
To improve rat embryo culture conditions, responses of Wistar 2-cell embryos from 2 breeders to oxygen tension (5 vs 20%) and bovine serum albumin (BSA) (0 vs 3 mg/ml) were examined using rat 1-cell embryo culture medium (mR1ECM). Supplementation of 3 mg/ml BSA significantly stimulated and accelerated development to the blastocyst and expanded blastocyst stages during 72 and 96 h culture, while reduced oxygen tension stimulated cell division. Fetus development after transfer of blastocysts obtained from 72 h culture under 5% O2 with BSA was significantly higher than those cultured under atmospheric oxygen without BSA. However, the nuclear numbers of in vitro cultured blastocysts and fetus development after embryo transfer were still significantly lower than in vivo developed blastocysts, indicating the current culture condition is still suboptimal.
A genetic linkage map for Suncus murinus was previously constructed with 11 marker loci. In this study, we developed 172 new microsatellite and three RFLP markers, and re-constructed a new framework map by combining all markers. The new map comprises 42 markers that are distributed into 12 linkage groups, two of which are assigned to chromosomes, and spans 403.5 cM with an average inter-marker distance of 13.5 cM.
The OLETF rat is a well-established model for the study of type 2 diabetes associated with obesity and has been shown to possess multiple hyperglycemic alleles in its genome. Here we focused on and carefully characterized one of the previously reported congenic strains, F.O-Nidd3/of that carries the OLETF allele of the Nidd3/of locus (also known as Niddm21 in the Rat Genome Database) in the normoglycemic F344 genetic background. A prominent finding was that the F1 progeny between the congenic and the F344 stain, whose genotype is heterozygote at the Nidd3/of locus, showed mild hyperglycemia equal to the parental congenic rat, suggesting that the OLETF allele is dominant. To our knowledge, this is the first study in which a diabetic QTL has been directly demonstrated to be dominant by using congenic strains.
Shin Nippon Biomedical Laboratories, Ltd. (SNBL) imported and quarantined 3,148 cynomolgus monkeys (aged 2.5 to 6.5 years) from China in 2002. The hematology and blood biochemistry data obtained from these monkeys on Day 32 of quarantine were analyzed separately by sex [2,890 animals in which no abnormalities were observed during the 35-day quarantine period (normal group), and 258 animals which exhibited diarrhea 1 to 12 times (diarrhea group)]. The values obtained for all parameters were within the normal range (mean ± SD), and no significant abnormalities were noted in either sex. The clinical pathology data from 11 animals (6 males and 5 females) exhibiting diarrhea repeatedly (10 to 12 times) were statistically analyzed, and significant differences were noted in PLT and ALP in both sexes. The PLT values of these animals were within the normal group mean ± 2 SD, and were considered within the normal range. A significant difference was noted in some individual ALP values (males: Nos. 2 and 3, females: Nos. 1, 3, and 4). The clinical pathology data obtained from the normal group in this study basically correspond to the widely reported results already obtained from healthy cynomolgus monkeys, from which it can be concluded that the cynomolgus monkeys from China were generally healthy and presenting no particular abnormality. The clinical pathology data from the normal group will serve as valuable baseline data for experimenters using cynomolgus monkeys.
Production efficiency of transgenic rats was compared directly between the routine pronuclear microinjection of exogenous DNA solution (PNMI-Tg method) and the ooplasmic injection of sperm cells exposed to exogenous DNA solution (ICSI-Tg method) using six DNA constructs. The overall production efficiency per treated oocyte in the ICSI-Tg method (mean 1.1%, range 0.2 to 3.1%) was similar to that in the PNMI-Tg method (mean 1.1%, range 0 to 2.4%). An advantage of the ICSI-Tg method in the production of transgenic rats is noted in cases in which a low yield of pronuclear zygotes is an inevitable fate of the rat strain.
In this study, the influence of pregnancy and parturition on mice in a mouse model of latent infection with Pseudorabies virus (PrV) was analyzed. Latently infected (LI) female mice were paired with mature uninfected males. The mating produced progeny without any clinical signs of Aujeszky's Disease. At weaning, both male and female progeny of LI mice showed significantly lower weight than control mice. PrV was not detected from nasal swab specimens of the female parent mice or the trigeminal ganglia of all mice, except 3 of 50 neonatal mice. These findings demonstrate that pregnancy and parturition induce little reactivation of latent PrV, but do affect the mother's body, as indicated by the decreased weight of progeny at weaning.
The non-coding RNA Xist is indispensable for X chromosome inactivation. Transcriptional control of Xist gene depends on its antisense partner gene Tsix which prevents Xist up-regulation in cis. Previous studies proposed Tsix acts by regulating chromatin structure. Although histone modifications in the Xist locus during differentiation have been described in female embryonic stem (ES) cells, they remain unclear in males. Here we addressed histone modifications in the Xist locus in wild-type and Tsix-mutant male ES cells during differentiation. Their active and repressive modifications were attenuated upon differentiation, while the histone modification profile in males resembled that of females in an undifferentiated condition. These results provide implications in understanding the regulation of Xist gene, as well as other developmentally regulated genes, through chromatin structure.
CBy.ALY-aly/aly (C-aly) mice develop progressive dermatitis in areas of the face and dorsal neck from around three months of age. Staphylococcus aureus was detected in the skin lesions of C-aly mice. However, even when the mice were raised under S. aureus free conditions, a similar, though less severe, dermatitis was still observed. The mice showed a marked increase in the number of eosinophils in the peripheral blood and skin lesions, with no changes in plasma IgE levels. These findings suggest that the dermatitis of these mice may be an atypical allergic condition with little or no involvement of IgE. C-aly mice may be a useful animal model of chronic dermatitis or pruritus without elevated IgE levels.