Diet-induced type II diabetes in C57BL/6J mice

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg/dl and blood insulin levels of greater than 150 microU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.     

Control of expression of insulin resistance and hyperglycemia by different genetic factors in diabetic C57BL/6J mice

The inheritance of the tendency to develop diet-induced non-insulin-dependent (type II) diabetes was analyzed in crosses between diabetes-prone C57BL/6J (BL/6) mice and diabetes-resistant A/J mice. The effects of a diabetogenic diet on blood glucose and insulin levels, insulin sensitivity, and weight were evaluated in F1 and both (BL/6 X A/J) F1 X BL/6 and (BL/6 X A/J) F1 X A/J backcross mice. These results suggest that diet-induced hyperglycemia is largely determined by a recessive gene and diet-induced insulin resistance by a dominant gene. Analyses of both backcrosses indicated that insulin sensitivity and blood glucose levels were unrelated, suggesting that they are controlled by different genetic factors. This conclusion was supported by data from nine recombinant inbred BXA strains in which no correlation was observed between these variables. Furthermore, insulin sensitivity and body weight correlated differently in the two backcross groups, suggesting that insulin resistance is not simply a function of obesity. The number of genes that predominantly influence diabetic traits was estimated by comparing the variance observed in (BL/6 X A/J) F1 X BL/6 backcross mice with that observed in parental mice. The data suggest that relatively few genes predominantly affect the diabetic phenotype in this murine model.     

Expression of type X collagen in young and old C57Bl/6 and Balb/c mice. Relation with articular cartilage degeneration

OBJECTIVE: To investigate whether the development of osteoarthritic lesions in the knee joints of mice is associated with increased immunostaining of type X collagen. METHODS: Sections of total knee joints in combination with immunohistochemistry were used to study the distribution of type X collagen in the cartilage of young and old mice of two mouse strains, Balb/c and C57Bl/6, known to develop osteoarthritic lesions at different locations. Expression of type X collagen and PTH/PTHrP-receptor mRNA were studied by RT-PCR. RESULTS: Young adult Balb/c and C57Bl/6 mice both expressed type X collagen in the non-calcified cartilage of the tibia-femoral joint. Old mice of both strains had a strongly increased deposition of type X collagen in the patella-femoral but not in the tibia-femoral joint. The locations in the murine knee joints prone to develop osteoarthritis (OA) did not preferentially express increased amounts of type X collagen. Thus, whereas increased type X was observed in both strains in the patella-femoral joints, only Balb/c mice preferentially developed osteoarthritic lesions in these joints. Also cartilage degeneration was usually seen only in the lateral compartment of the knee joints of C57Bl/6 mice but this was not accompanied by increased type X collagen immunostaining. Increased deposition of type X collagen was not associated with elevated levels of type X collagen mRNA or with decreased levels of PTH/PTHrP-receptor mRNA. CONCLUSION: Type X collagen expression and spontaneous OA in mice are not necessarily related since OA prone locations in the murine knee joint do not preferentially express type X collagen.     

C57BL/6 and 129/Sv mice: genetic difference to renal ischemia-reperfusion

Background: C57BL/6 and 129/Sv are the 2 most commonly used strains of mice in renal ischemia-reperfusion injury (IRI) studies, yet there are currently no studies that contrast differences in the degree of renal injury after ischemia-reperfusion. Methods: To evaluate renal IRI in male C57BL/6 and 129/Sv mice, we performed unilateral clamping of the left renal pedicle for 45 minutes and compared the degree of renal tissue damage and function. To measure function and tissue damage we examined: glomerular filtration rate (GFR; by inulin clearance), renal blood flow (RBF; by p-aminohippurate [PAH] clearance), renal morphology, immunohistochemistry for infiltrating leukocytes, and fibrogenic markers by Sirius red staining. Results: After unilateral IRI, 129/sv mice had significantly less GFR and RBF disfunction at both day 14 (d14) and d28. 129/sv mice also had significantly less acute tubular necrosis on d1 and fewer infiltrating leukocytes on d28, as well as less collagen deposition on d28 than C57BL/6 mice. Conclusions: C57BL/6 mice were much more sensitive to damage caused by renal IRI than are 129/Sv mice.     

Rapid development of severe end-organ damage in C57BL/6 mice by combining DOCA salt and angiotensin II

The C57BL/6 mouse strain serves as the genetic background of many transgenic and gene knockout models; however, this strain appears to be resistant to hypertension-induced renal injury. We developed a new model of hypertensive end-organ damage in C57BL/6 mice by combining deoxycorticosterone acetate (DOCA) and salt with angiotensin II infusion. The systolic blood pressure (SBP) was significantly elevated in DOCA salt-angiotensin II mice compared to control mice or mice treated individually with DOCA salt or angiotensin II. Hypertensive glomerular damage, increased expression of profibrotic and inflammatory genes, albuminuria, tubular casts, increased plasma cholesterol, cardiac hypertrophy, and fibrosis were found in mice treated with DOCA salt-angiotensin II. The SBP in the angiotensin II-infused group was further increased by increasing the infusion rate; only mild injury was observed in these mice, suggesting that blood pressure was not a causal factor. Removal of DOCA and the angiotensin pump lowered blood pressure to normal; however, albuminuria along with the glomerular and cardiac damage did not completely resolve. Our study describes a new model of hypertensive end-organ damage and repair in C57BL/6 mice.     

Rejection of C57BL/6 skin grafts by (C57BL/6 X Mus musculus castaneus)F1 hybrids.

Hybrid offspring from C57BL/6(B6) females mated to males of the subspecies Mus musculus castaneus received B6 skin grafts. No strong Y chromosome-linked histocompatibility genes were detected, although occasional rejection of parental grafts by both male and female hybrids was observed after long periods. Rejection was attributed to interaction of B6 and Castaneus-derived genes in the hybrids.     

胸腺内注射可溶性异基因主要组织相容性复合物抗原诱导皮肤移植特异性耐受

用３ｍｏｌ／ＬＫＣｌ从Ｃ５７ＢＬ／６小鼠脾细胞提取可溶性主要组织相容性复合物（ＭＨＣ）抗原，注射到ＢＡＬＢ／Ｃ受体鼠胸腺内，诱导了成年小鼠对该异基因小鼠皮肤移植物的耐受。除在胸腺注射当天及第３天给予抗Ｔ细胞单克隆抗体外，不使用免疫抑制剂。实验组移植皮肤平均存活时间（ＭＳＴ）为８３天，对照组ＭＳＴ为１１天。诱导耐受的小鼠对第３供体的移植皮肤仍正常排斥（ＭＳＴ为１２天）。单向混合淋巴细胞反应，耐受小鼠脾脏淋巴细胞对特异供体的脾细胞无反应，对第３供体的脾细胞反应正常，对丝裂原刺激的增殖反应正常。显示诱导的耐受是供体特异性的，无非特异性免疫抑制。     

Optimizing suture middle cerebral artery occlusion model in C57BL/6 mice circumvents posterior communicating artery dysplasia

The suture middle cerebral artery occlusion (MCAO) model is used worldwide in both academia and industry. However, the variable occurrence of dysplasia in posterior communicating arteries (PcomAs) induces high mortality and instability in permanent MCAO models, limiting the model's application to transient focal ischemia. In particular, high mortality in intraluminal suture MCAO models is associated with the dysplasia of PcomAs in C57BL/6 mice. Optimization of silicone coating length is critical for reducing mortality and generating stable infarct in this model. The aim of our study is to reduce mortality and improve the reproducibility of the intraluminal suture MCAO model in C57BL/6 mice, which have high variation in PcomA dysplasia. Adult male C57BL/6 mice (n=38) underwent MCAO using sutures with various diameters and silicone coating lengths. The occlusion of cerebral vessels was examined by synchrotron radiation live angiography. The morphology of PcomAs was examined under a microscope after MICROFIL(?) infusion. Neurological outcome, infarct volume, and mortality were examined within 28 days. Optimizing the silicone coating on an 8-0 suture tip, we were able to reduce the model mortality to zero after permanent occlusion in C57BL/6 and produce stable brain infarct volume independent of the patency of PcomAs.     

C57BL/6j小鼠异种移植瘤模型的建立

目的 建立C57BL/6j小鼠人神经母细胞瘤移植瘤模型.方法 取对数生长期SK-N-SH细胞1×107个/ml,分别接种3 d、7 d、3周、4周、5周、6周、7周C57BL/6j系小鼠及6周BALB/C系裸鼠,观察小鼠成瘤率、相对肿瘤体积(RTV)、相对肿瘤增长速率(K)、相对肿瘤倍增时间(Td)、宿主存活时间及移植瘤病理学情况.结果 C57BL/6j各年龄段及BALB/C持续成瘤率分别为:100%、100%、90%、70%、60%、0%、0%、100%.3周龄C57BL/6j与BALB/C比较RTV、K、Td及存活时间均差异无统计学意义(P＞0.05).结论 在C57BL/6j小鼠体内成功建立人类异种移植瘤模型,3周龄为最适宜接种时间点.

Abstract：

Objective To investigate the feasibility of human neuroblastoma xenograft model in C57BL/6j mice. Methods Three-day, 7-day, 3-week, 4-week, 5-week, 6-week and 7-week age C57BL/6j and 6-week age BALB/C nude mice were subcutaneously inoculated with 1 × 107 cell/ml SK-NSH cells in logarithmic phase, respectively. The tumor generation rate, relative tumor volume ( RTV), relative growth rate (K), relative doubling time (Td), survival time and pathological changes were tested.Results The continuing tumor generation rate of C57BL/6j mice and BALB/C nude mice was 100% (10/10) at the 3rd day, 100% (10/10) at the 7th day, 90% (9/10) at the 3rd week and 70% (7/10) at the 4th week, 60%(6/10) at the 5th week, 0%(0/10) at the 6th week, 0%(0/10) at the 7th week, and 100% (10/10) at the 6th week, respectively. There was no significant difference in RTV, K, Td, and survival time (P＞0.05) between 3-week age C57 BL/6j mice and BALB/C nude mice. Conclusion Human neuroblastoma xenograft models were successfully established the in C57BL/6j mice, and 3-week age was the most appropriate opportunity of vaccination.     

Strain differences in bone density and calcium metabolism between C3H/HeJ and C57BL/6J mice.

Previous reports indicate that peak bone density is significantly higher in C3H/HeJ (C3H) than in C57BL/6J (C57BL) mice, making these two inbred strains useful models for studying the genetic basis for peak bone density. The following study was undertaken to examine whether strain differences in the bone density of C3H and C57BL mice are associated with differences in intestinal calcium (Ca) absorption. Calcium absorption was measured by the balance technique and animals received two injections of fluorochromes 5 days apart before killing. Subsequently, the femurs were removed and, following measurement of volumetric density, the left femur was divided into three equal parts and the middle third served as the femoral cortical diaphysis. Femur diaphyseal volumetric bone density, ash, and Ca content were 10%, 29%, and 29% higher in C3H than in C57BL mice (p < 0.001), respectively. Bone length, periosteal mineral apposition rate, and periosteal bone formation rate of femoral diaphyseal cortical bone were not significantly different between the two strains of mice, but the marrow area of C57BL mice was almost twofold that of C3H mice (p < 0.0001). Intestinal Ca absorption and 1,25-dihydroxyvitamin D [1,25(OH)2D]-stimulated Ca2+ uptake by intestinal mucosal cells were 38% and 51% higher in C3H than in C57BL mice p < 0.001), respectively. Serum Ca and 1,25(OH)2D levels were 6% and 32% higher in C3H than in C57BL mice (p < 0.001), respectively, and the number of intestinal-occupied vitamin D receptors was 51% higher in C3H than in C57BL mice (p < 0.01). In a second experiment, three groups of C3H mice and three groups of C57BL mice were fed diets that contained 0.4%, 0.1%, or 0.02% Ca, and serum Ca, 1,25(OH)2D, parathyroid hormone (PTH), and intestinal Ca absorption measured. At all dietary Ca levels, C3H mice maintained positive Ca absorption and absorbed significantly more Ca than C57BL mice. In contrast, at low dietary Ca levels (0.1% and 0.02% Ca), C57BL mice maintained negative Ca absorption. Low dietary Ca increased serum PTH significantly in C57BL but not in C3H mice, and decreased serum 1,25(OH)2D and Ca levels in both strains of mice. Our findings indicate that the C57BL mice relied more on the mobilization of Ca from bone to maintain extracellular Ca homeostasis than the C3H mice. We conclude that strain differences in bone mass and density between C3H and C57BL mice is expressed, in part, through the vitamin D and PTH endocrine systems and their effects on the maintenance of extracellular Ca homeostasis.     

Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice.

Although the precise mechanisms contributing to insulin resistance and type 2 diabetes are unknown, it is believed that defects in downstream components of the insulin signaling pathway may be involved. In this work, we hypothesize that a serine/threonine kinase, glycogen synthase kinase-3 (GSK-3), may be pertinent in this regard. To test this hypothesis, we examined GSK-3 activity in two inbred mouse strains known to be susceptible (C57BL/6J) or resistant (A/J) to diet-induced obesity and diabetes. Examination of GSK-3 in fat, liver, and muscle tissues of C57BL/6J mice revealed that GSK-3 activity increased twofold in the epididymal fat tissue and remained unchanged in muscle and liver of mice fed a high-fat diet, compared with their low-fat diet-fed counterparts. In contrast, GSK-3 activity did not change in the epididymal fat tissue of A/J mice, regardless of the type of diet they were fed. In addition, both basal and diet-induced GSK-3 activity was higher (2.3- and 3.2-fold, respectively) in the adipose tissue of C57BL/6J mice compared with that in A/J mice. Taken together, our studies suggest an unsuspected link between increased GSK-3 activity and development of insulin resistance and type 2 diabetes in fat tissue of C57BL/6J mice, and implicate GSK-3 as a potential factor contributing to susceptibility of C57BL/6J mice to diet-induced diabetes.     

Genetic background differences between FVB and C57BL/6 mice affect hypnotic susceptibility to pentobarbital, ketamine and nitrous oxide, but not isoflurane

BACKGROUND: Pharmacogenomics has allowed us to identify the mechanisms underlying much of the inherited variability in drug response. There have been several reports of strain-dependent anesthetic actions in rodents, indicating that significant genetic differences exist in the hypnotic and antinociceptive effects of various anesthetics. METHODS: Loss of righting reflex was used to compare the hypnotic action of pentobarbital, ketamine, nitrous oxide and isoflurane between two genetically different populations of mice, C57BL/6 with black hair and Friends virus B (FVB) with white hair. RESULTS: C57BL/6 mice were more susceptible than FVB mice to the hypnotic effects of ketamine, pentobarbital and nitrous oxide. However, the sensitivity to isoflurane did not differ between C57BL/6 and FVB mice. CONCLUSION: Genetic background affects the hypnotic susceptibility to some anesthetic agents in mice. Our results indicate that there may be a different genetic basis for the operation of hypnosis between isoflurane and other anesthetics, such as pentobarbital, ketamine and nitrous oxide.     

Assessment of peripheral tolerance in anti-CD4 treated C57BL/6 mouse heart transplants recipients.

The study was designed to compare second heart and skin grafts and in vitro assays as a means of assessing peripheral tolerance in C57BL/6 mice. Vascularized heterotopic BALB/c hearts were placed in C57BL/6 recipients treated with anti-CD4, GK1.5 (1 mg total per 20 g mouse i.p. on days 0, 1, 2, 3). Those mice in which hearts survived for >60 days were challenged with donor and third-party (CBA) skin grafts or with second heart grafts, of donor or third-party origin, attached to the carotid artery and jugular vein. In vitro alloreactivity was assessed by mixed lymphocyte reactions (MLR) and cell mediated lympholysis (CML) using recipient spleen cells. Parenchymal damage, cellular infiltration and vascular disease were assessed from the histology of long-term allografts and isografts. Allografts in untreated recipients were rapidly rejected while isografts survived > 100 days. Primary allografts in anti-CD4 treated recipients also survived > 100 days, as did donor strain secondary heart transplants given at >60 days after the first graft. Third-party hearts were rapidly rejected, as were donor and third-party skin grafts placed on recipients with long-term allografts. These recipients showed low MLR response to both donor and third-party stimulators and donor-specific suppression of CML at 60 days post graft. Long-surviving heart allografts all showed evidence of parenchymal damage and vascular intimal thickening. Thus in the BALB/c to C57BL/6 donor-recipient strain combination, hearts, but not skin grafts, could be used to demonstrate peripheral tolerance, which seemed to be both organ and major histocompatibility complex (MHC) specific. Despite long survival, BALB/c hearts all showed evidence of parenchymal damage and vascular intimal thickening, a sign of chronic rejection.     

Age-related changes in trabecular architecture differ in female and male C57BL/6J mice.

We used microCT and histomorphometry to assess age-related changes in bone architecture in male and female C57BL/6J mice. Deterioration in vertebral and femoral trabecular microarchitecture begins early, continues throughout life, is more pronounced at the femoral metaphysis than in the vertebrae, and is greater in females than males. INTRODUCTION: Despite widespread use of mice in the study of musculoskeletal disease, the age-related changes in murine bone structure and the relationship to whole body BMD changes are not well characterized. Thus, we assessed age-related changes in body composition, whole body BMD, and trabecular and cortical microarchitecture at axial and appendicular sites in mice. MATERIALS AND METHODS: Peripheral DXA was used to assess body composition and whole body BMD in vivo, and microCT and histomorphometry were used to measure trabecular and cortical architecture in excised femora, tibia, and vertebrae in male and female C57BL/6J mice at eight time-points between 1 and 20 mo of age (n = 6-9/group). RESULTS: Body weight and total body BMD increased with age in male and female, with a marked increase in body fat between 6 and 12 mo of age. In contrast, trabecular bone volume (BV/TV) was greatest at 6-8 wk of age and declined steadily thereafter, particularly in the metaphyseal region of long bones. Age-related declines in BV/TV were greater in female than male. Trabecular bone loss was characterized by a rapid decrease in trabecular number between 2 and 6 mo of age, and a more gradual decline thereafter, whereas trabecular thickness increased slowly over life. Cortical thickness increased markedly from 1 to 3 mo of age and was maintained or slightly decreased thereafter. CONCLUSIONS: In C57BL/6J mice, despite increasing body weight and total body BMD, age-related declines in vertebral and distal femoral trabecular bone volume occur early and continue throughout life and are more pronounced in females than males. Awareness of these age-related changed in bone morphology are critical for interpreting the skeletal response to pharmacologic interventions or genetic manipulation in mice.     

Mitigation of graft-versus-host disease in lethally irradiated mice grafted with spleen cells adherent to glass beads.

Murine spleen cells were separated on the basis of adherence to glass beads into distinct subpopulations that differ in their ability to produce acute graft-versus-host disease (GVHD). Nonadherent CBA spleen cells produce acute GVHD in 6-10 days in lethally irradiated (C57BL/6 X CBA)F1 mice as do unfractionated spleen cells. Spleen cells which are adherent to glass beads, however, enable 71% of the mice to survive without symptomatology of acute GVHD. The low proliferative response of these cells to phytohemagglutinin (PHA) correlated with the mitigated GVHD seen in animals grafted with this fraction. Proliferative cells as determined by the spleen colony assay and the in vitro agar colony-forming assay are present in this fraction as are cells responsive to mitogenic stimulation with lipopolysaccharide (LPS). B6CBF1 mice grafted with CBA adherent cells exhibit a gradual return over a period of 5 months to normal PHA and LPS stimulation levels as shown by splenic cell responses of these mice to mitogens. Surviving mice grafted with adherent cells were chimeric as determined by electrophoretic hemoglobin pattern analysis and serial bone marrow transplantation.     

Effect of helper and/or cytotoxic T-lymphocyte depletion on low-dose streptozocin-induced diabetes in C57BL/6J mice

The low-dose streptozocin (STZ) model of diabetes has been reported to involve direct STZ beta-cytotoxicity and/or immunologically mediated beta-cell destruction. Because the T-lymphocyte dependency of such a model is controversial, we further assessed the role of T-lymphocytes by determining the occurrence and magnitude of hyperglycemia as well as the pancreatic insulin contents in both STZ-injected nude C57BL/6J male mice and STZ-injected euthymic C57BL/6J male mice selectively depleted in helper and/or cytotoxic T-lymphocytes with monoclonal antibodies (MoAbs). The effectiveness of MoAb treatment was assessed in lymph node cells by flow-microfluorometry analysis and in spleen cells by concanavalin A stimulation, allospecific cytotoxic T-lymphocyte activity, and T-lymphocyte lymphokine production. Sixteen days after the first STZ injection, hyperglycemia (plasma glucose greater than 200 mg/dl) occurred in significantly fewer helper T-lymphocyte-depleted mice (P less than .005) or helper and cytotoxic T-lymphocyte-depleted mice (P less than .001) than in non-MoAb-treated mice. However, a progressive increase in the number of mice with hyperglycemia ensued in all MoAb-treated groups, and 2 mo after STZ was administered, the prevalence of hyperglycemia, mean plasma glucose levels, and pancreatic insulin contents did not differ significantly from the values obtained in the non-MoAb-treated animals. Similarly, STZ-injected C57BL/6J male nude mice developed hyperglycemia that was associated with a marked decrease in pancreatic insulin contents on a time course comparable with that of STZ-injected euthymic C57BL/6J male mice depleted in helper or in helper and cytotoxic T-lymphocytes by MoAbs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tolerance, immunocompetence, and secondary disease in fully allogeneic radiation chimeras

The aim of this study was to ascertain the extent to which secondary disease and mortality in fully allogeneic chimeras (C57BL leads to CBA) is caused (if at all) by a delayed graft-versus-host reaction. Adult CBA males were thymectomized, irradiated, and reconstituted with T-lymphocyte-depleted C57BL or CBA bone marrow cells (BMC), followed three weeks after irradiation by implantation under the kidney capsule of thymic lobes from C57BL or CBA fetal or adult donors. These mice were observed for the development of secondary disease for periods in excess of 250 days, and they were examined at 5 weeks or 4 months for T lymphocyte reactivity and tolerance to alloantigens, using the cell-mediated lympholysis assay (CML). The following results were obtained. First, removal of T lymphocytes with anti-Thy 1 antibody and complement from allogeneic bone marrow did not prevent wasting and eventual death, although it prolonged the lifespan of mice substantially. Second, T lymphocytes generated from bone marrow-derived precursor cells became tolerant of the histocompatibility antigens of the thymus donor strain but remained normally reactive to third-party antigens. Third, allogeneic radiation chimeras did not survive as well as animals reconstituted with syngeneic cells, even when they were demonstrably tolerant in CML. Fourth, C57BL BMC maturing in a CBA host equipped with a C57BL thymus graft did not become tolerant of host antigens, indicating that extra-thymic tolerance does not occur in fully allogeneic--as opposed to semiallogeneic--chimeras. It is argued that the function of B lymphocytes and/or accessory cells is impaired in fully allogeneic radiation chimeras, and that the mortality observed was directly related to the resulting immunodeficiency. The relevance of the results described in this paper to clinical bone marrow transplantation is discussed.     

C57BL/6小鼠前列腺癌原位细胞移植动物模型的建立

目的 建立一种C57BL/6小鼠前列腺癌原位细胞移植动物模型.方法 C57BL/6小鼠30只,用微量注射器分别将0.5×106个RM-1细胞注射入前列腺左、右背侧叶包膜下.每3 d随机处死5只小鼠,动态观察小鼠前列腺癌局部生长、盆腔淋巴结转移和器官转移;术后15 d处死小鼠后,剩余5只常规饲养直至死亡,观察小鼠的平均荷瘤生存期.结果 C57BL/6小鼠前列腺原位移植RM-1细胞后第3、6、9、12、15天前列腺体积组间差异有统计学意义(P＜0.01);术后第12天开始,出现明显尿潴留、双侧或单侧输尿管扩张、肾脏体积增大、肾盂扩张;组织学观察发现术后前列腺癌细胞逐渐取代正常的前列腺组织,术后第12天组可见肿瘤侵犯周围肌肉,术后第15天组可见肿瘤侵犯精囊和膀胱.术后第3、6、9天未见明显盆腔淋巴结转移,第12、15天盆腔淋巴结转移率均为80%.各组均未发现明显的远处器官转移.各组小鼠成瘤率均为100%.小鼠平均荷瘤生存期为(15.60±0.89)d.结论 虽然未见明确的器官转移情况,但该模型能够较好的模拟人类前列腺癌的发生、发展、局部侵袭及淋巴转移的过程,是一种较理想的前列腺癌动物模型.

Abstract：

Objective To investigate the regularity in establishing the prostate cancer orthotopic transplantation model in C57BL/6 mice. Methods RM-1 cells (0.5×106)were injected into the right and left dorsal lateral prostate capsules of 30 C57BL/6 male mice respectively using micro-syringe. Five mice were sacrificed every three days to observe the local growth, the occurrence and development of prostate cancer, and the remaining five mice were fed to death to calculate the average survival period of tumorbearing mice. Results The volume of prostates was significantly different among the five groups. From the 12th day, significant retention of urine, ureterectasia (bilateral or unilateral ), increased kidney volume and pelviectasis were observed. The rate of tumor formation in the five groups which included the 3rd, 6th,9th, 12th d and 15th day was all 100%. HE staining showed that prostate cancer cells gradually replaced the normal prostate tissue. At the 12th day, muscle tissue around prostate was invaded by prostate cancer.In some samples there was metastasis of seminal vesicles and bladder at the 15th day. The rate of metastasis in pelvic lymph nodes at the 12th or 15th day was 80%. The average survival period of tumor-bearing mice was (15.60±0.89) days. Conclusion The prostate cancer orthotopic transplantation model in C57BL/6 mice can better simulate the process of occurrence, development, local invasion and lymph node metastasis of human prostate cancer and be suitably used as a model of prostate cancer research.     

Thyroid graft rejection between C57BL/6 and H-2Kb mutant mice. Differences in the immunogenic expression of the mutated molecule on thyroids of six different mutants

Mice that possess mutations in the H-2 region were selected by means of skin grafting. We tested the survival time of thyroid grafts transplanted between C57BL/6 mice and their descendent H-2Kb mutant mice and compared the kinetics of skin versus thyroid graft rejection in each of the mouse strain combinations tested. The results demonstrated that reciprocal thyroid grafts between C57BL/6 mice and bm1, bm3, bm4, bm5, and bm6 mutants are accepted for long periods. The bm8 mutant appeared to be an exception because a small fraction of reciprocal thyroid grafts were rejected between bm8 and C57BL/6 mice. Transplantation of C57BL/6 mice with skin grafts from bm1, bm3, bm4, and bm8 donors induced rejection of subsequent thyroid grafts syngeneic with the skin. Thyroid grafts of bm5 and bm6 were not rejected by C57BL/6 mice even after preimmunization with bm5 and bm6 skin grafts. In contrast to skin grafts, innoculation of C57BL/6 mice with 50 X 10(6) spleen cells from mutant mice failed to immunize the recipients and induce rejection of mutant thyroid grafts. The results indicate that skin graft rejection assays and in vitro cell-mediated lympholysis (CML) typing can not always predict the consequence of transplantation of organs such as thyroid, and also that alterations in the H-2Kb molecule as a result of spontaneous mutations can give rise to mutated molecules that differ in their immunogenic and antigenic properties when expressed on thyroid cells, as compared with skin.