应用环磷酰胺构建C57BL/6J小鼠免疫抑制模型

背景：在免疫增强剂的研究中,常用到免疫抑制模型,如何建立免疫抑制模型成为免疫增强剂作用评价的关键。 目的：应用环磷酰胺构建C57BL/6J小鼠免疫抑制模型。 方法：将小鼠随机分为正常对照组、环磷酰胺50 mg/kg 5 d组,环磷酰胺80 mg/kg 3 d组,环磷酰胺80 mg/kg 5 d组,环磷酰胺100 mg/kg 5 d组和环磷酰胺100 mg/kg隔天给药组。正常对照组小鼠腹腔注射生理盐水0.1 mL,连续5 d。环磷酰胺50 mg/kg 5 d组,环磷酰胺80 mg/kg 3 d组,环磷酰胺80 mg/kg 5 d组和环磷酰胺100 mg/kg 5 d组小鼠分别以环磷酰胺50,80,80,100 mg/kg腹腔注射连续5,3,5,5 d。环磷酰胺100 mg/kg隔天给药组小鼠腹腔注射100 mg/kg环磷酰胺,隔天1次,共注射3次。 结果与结论：与正常对照组比较,腹腔注射环磷酰胺可导致小鼠外周血中CD3⁺T,CD3⁺CD4⁺T及CD3⁺CD8⁺T细胞明显下降(P < 0. 05);谷丙转氨酶(除环磷酰胺50 mg/kg 5 d、80 mg/kg 3 d组)、谷草转氨酶、尿素显著升高(P < 0.05),其中环磷酰胺80 mg/kg 5 d组、环磷酰胺100 mg/kg 5 d组和环磷酰胺100 mg/kg隔天给药组对肝肾功能的影响更为明显。提示腹腔注射环磷酰胺可建立CD3⁺T,CD3⁺CD4⁺T及CD3⁺CD8⁺T细胞明显下降的免疫抑制模型,其中以环磷酰胺50 mg/kg 5 d和80 mg/kg 3 d方式对肝肾功能的损伤较小。     

Spontaneous central apneas occur in the C57BL/6J mouse strain

Despite the clinical significance of central apneas in a wide range of disorders little is known about their pathogenesis. Research in this field has been hindered by the lack of appropriate animal models. Our goal was to determine whether the C57BL/6J mouse strain, which has an inherited predisposition for dysrhythmic breathing, exhibits spontaneous apneas. In vivo plethysmography of unanesthetized, unrestrained adult C57BL/6J mice revealed a regular occurrence of spontaneous apneas. In situ recordings from respiratory outputs (phrenic, vagal, hypoglossal nerves) in the working heart-brainstem preparation (WHBP) also showed spontaneous central apneas accompanied by laryngeal closure as indicated by tonic vagal postinspiratory activity and increase in subglottal pressure. The apneas were further characterized by a hypoglossal discharge with delayed onset compared to the tonic vagal postinspiratory activity. We conclude that spontaneous central apneas with active laryngeal closure occur in C57BL/6J mice. This mouse strain is a useful animal model to study neuronal mechanisms that underlie the generation of spontaneous central apneas.     

Diverse effects of stanozolol in C57BL/6J and A/J mouse strains

Although skeletal muscle is the principal target for androgenic anabolic steroids (AAS) other physiological and behavioral processes are also affected. Wide variations in response to AAS are known to exist in individuals but the genetic basis of this has hardly been explored. Female mice from the A/J and C57BL/6J strains were divided into four experimental groups: CTRL-Sham, housed in a regular mouse cage and subjected to a sham operation mimicking implantation of steroids; CTRL-AAS, mice similarly housed and implanted with a pellet containing stanozolol (release rate, 4.6 mg/kg/day); EX-Sham, sham operated mice housed in a cage with two towers which required mice to climb 1 m to obtain food or water; EX-AAS, mice similarly housed and implanted with a stanozolol pellet. The experimental treatment was initiated at 10 weeks of age and lasted for 7 weeks. Body weight was assessed periodically during the experiment (time effect), systolic blood pressure (BP) and heart rate (HR) were measured after 6 weeks of treatment, and weights of gastrocnemius (GAST), soleus, tibialis anterior (TA), extensor digitorum longus (EDL), quadriceps femoris (QF) and biceps brachii (BB) muscles, heart, liver, kidney and abdominal fat were measured after 7 weeks of treatment. AAS treatment significantly increased weight of GAST (P ≪ 0.001), TA (P < 0.01), EDL (P < 0.01) and QF (P ≪ 0.001) muscles in both of the strains. Several of the measured indices were differentially affected in the two strains by AAS (body weight, Time × Strain × AAS P < 0.02; BP and HR, Strain × AAS P < 0.03 and P < 0.01, respectively). These findings encourage the view that recombinant inbred strains and chromosome substitution strains derived from the A/J and C57BL/6J mice can be utilized to explore the genetic architecture of these interactions in order to elucidate the mechanism underlying both the positive and negative health-related effects of AAS.     

Age-dependent and tissue-specific structural changes in the C57BL/6J mouse genome

We tested the hypothesis that structural changes in the genome parallel age- and organ-specific phenotypes in conjunction with the differential transposition activities of retroelements. The genomes of the liver from C57BL/6J mice were larger than other organs, coinciding with an increase in genomic copies of certain retroelements. In addition, there were differential increments in the genome size of the liver with increasing age, which peaked at 5 weeks. The findings that the genome structure of an individual is variable depending on age and organ type in association with the transposition of retroelements may have broad implications in understanding biologic phenomena.     

Standard atlas space for C57BL/6J neonatal mouse brain

A standard atlas space with stereotaxic co-ordinates for the postnatal day 0 (P0) C57BL/6J mouse brain was constructed from the average of eight individual co-registered MR image volumes. Accuracy of registration and morphometric variations in structures between subjects were analyzed statistically. We also applied this atlas coordinate system to data acquired using different imaging protocols as well as to a high-resolution histological atlas obtained from separate animals. Mapping accuracy in the atlas space was examined to determine the applicability of this atlas framework. The results show that the atlas space defined here provides a stable framework for image registration for P0 normal mouse brains. With an appropriate feature-based co-registration strategy, the probability atlas can also provide an accurate anatomical map for images acquired using invasive imaging methods. The atlas templates and the probability map of the anatomical labels are available at .     

牛MBP诱导BALB/c和C57BL/6小鼠实验性变态性脑脊髓炎样反应的研究

为了进一步研究实验性变态反应性脑脊髓炎(EAE)动物模型,采用从新鲜牛脊髓中提取的MBP免疫诱导非敏感品系BALB/c小鼠和C57BL/6小鼠,通过对实验动物的症状、中枢神经系统的病理改变及细胞因子水平变化的检测,较成功地建立了C57BL/6、BALB/c小鼠的EAE模型,实验方法稳定可靠。     

APCMin/+结直肠癌癌前病变小鼠模型的生物学特性

目的 研究C57BL/6J-APCMin/+小鼠肠道腺瘤的生物学特性.方法 记录APCMin/+小鼠的繁育情况,通过统计不同周龄小鼠小肠及大肠腺瘤的数目和总体积,观察其肠道腺瘤的发生、发展规律;通过病理组织学切片,观察腺瘤的病理学变化;通过免疫组织化学染色,观察WNT信号通路相关基因的表达情况.结果 APCMin/+小鼠9周龄时肠道开始有腺瘤发生,24周龄时多数小鼠出现死亡.从9～24周龄,腺瘤体积持续增大,但小肠腺瘤数目不再增加.免疫组化染色显示腺瘤中β-catenin入核,启动WNT信号通路下游原癌基因cyclinD1活化.结论 APCMin/+小鼠是良好的结直肠癌前病变动物模型.     

A multimodal, multidimensional atlas of the C57BL/6J mouse brain

Strains of mice, through breeding or the disruption of normal genetic pathways, are widely used to model human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison. We have developed a digital atlas of the adult C57BL/6J mouse brain as a comprehensive framework for storing and accessing the myriad types of information about the mouse brain. Our implementation was constructed using several different imaging techniques: magnetic resonance microscopy, blockface imaging, classical histology and immunohistochemistry. Along with raw and annotated images, it contains database management systems and a set of tools for comparing information from different techniques. The framework allows facile correlation of results from different animals, investigators or laboratories by establishing a canonical representation of the mouse brain and providing the tools for the insertion of independent data into the same space as the atlas. This tool will aid in managing the increasingly complex and voluminous amounts of information about the mammalian brain. It provides a framework that encompasses genetic information in the context of anatomical imaging and holds tremendous promise for producing new insights into the relationship between genotype and phenotype. We describe a suite of tools that enables the independent entry of other types of data, facile retrieval of information and straightforward display of images. Thus, the atlas becomes a framework for managing complex genetic and epigenetic information about the mouse brain. The atlas and associated tools may be accessed at http://www.loni.ucla.edu/MAP.     

8-OH-DPAT suppresses spontaneous central apneas in the C57BL/6J mouse strain

Apneas are common and prognostically relevant disorders of the central control of breathing, but pharmacological interventions are dissatisfying. The respiratory phenotype of C57BL/6J mice is characterized by the occurrence of spontaneous central apneas with laryngeal closure. In the present study we investigated the impact of the 5-HT(1A) receptor agonist 8-OH-DPAT on apneas in C57BL/6J mice, because of the important role of serotonin in the regulation of breathing and previous reports showing that serotonergic drugs can affect central apneas. Whole-body plethysmography in awake, unrestrained mice revealed that intraperitoneal application of 8-OH-DPAT (10microgkg(-1)) decreased the occurrence of spontaneous apneas from 1.91+/-0.25 to 1.05+/-0.05 apneas min(-1). The efficacy of 5-HT(1A) receptor activation was further verified in the in situ working heart-brainstem preparation. Here the apneas occurred at a frequency of 1.33+/-0.19min(-1). Intra-arterial perfusion with 1-2microM 8-OH-DPAT completely abolished spontaneous apneas. These results suggest that 5-HT(1A) receptor activation may be a potential treatment option for central apneas.     

A mammary gland adenomyoepithelioma in a C57BL/6 mouse

Mammary gland adenomyoepitheliomas are benign complex mammary gland tumors composed of neoplastic cells of epithelial and myoepithelial origins, described in many species (humans, dogs, cats, rats) and rarely in mice. We report here an adenomyoepithelioma in a C57BL/6 female mouse. Histologically, tubes and cords formed by neoplastic epithelial cells were separated by bundles of neoplastic myoepithelial cells in a clear and partially mucinous matrix. The tumor displayed characteristics of a benign neoplastic proliferation with a compressive growth pattern, and moderate cellular pleomorphism and mitotic index. At immunohistochemistry, the epithelial cells were strongly cytokeratin positive; the myoepithelial cells were weakly cytokeratin positive and strongly smooth muscle actin positive. This is to our knowledge, the first report of a mammary gland adenomyoepithelioma in a C57BL/6 mouse.     

Development of inferior colliculus response properties in C57BL/6J mouse pups

Summary Response properties of inferior colliculus (IC) neurons were studied in tranquilized C57BL/6J mice during a period of rapid auditory system development between 12 and 17 days of age. In IC units of the youngest mice, spontaneous activity was absent, a disproportionate number of onset responses was observed, and many units were not securely driven by sound. Frequency response ranges were restricted to relatively low frequencies, sharpness of tuning was poor, and thresholds at best frequencies (BFs) were quite high. Dynamic intensity ranges were restricted, but nonmonotonic functions were observed. By 15–17 days of age, spontaneous activity was appreciable, incidences of response patterns were near adult proportions, and most units in the ventrolateral nucleus were securely driven by tones. Response ranges had expanded markedly to include high frequencies, sharpness of tuning increased, and thresholds had decreased. Dynamic intensity ranges and intensity functions were similar to those observed in adult mice.     

C57BL/6小鼠皮肤毛囊发育的实验研究

目的探讨胎鼠,乳鼠和成鼠毛囊发育的规律。方法石蜡和冰冻超薄切片,采用HE染色,AP活性染色,油红O染色,凋亡细胞鉴定等方法观察不同时期C57BL/6小鼠毛囊的发育情况。结果胚胎发育第15.5d(E15.5)开始出现毛囊,至E18.5胎鼠背部皮肤逐渐增厚,毛囊逐渐增多。乳鼠出生第1d毛囊大部分处于第4阶段之前,毛囊数量继续增加,至出生第4d皮肤基底层未见新生的毛囊,此时毛囊数量维持不变,出生第9d毛囊达到第8阶段。成鼠脱毛后第9d约有95%的毛囊进入生长Ⅳ期,第17d约有63.3%的毛囊进入退化期,第22d约有85%的毛囊处于退化期。结论小鼠毛囊的早期发育起始于E15.5,从E17.5到出生后3d毛囊数量呈快速增加趋势,因此,这一时期可以用于探讨毛囊再生机制等相关研究。     

Fatty acid bile acid conjugates inhibit atherosclerosis in the C57BL/6 mouse model.

OBJECTIVE: The aim of the current research was to study whether fatty acid bile acid conjugates (FABACs) have a beneficial effect on atherosclerosis progression and blood lipid levels in mice. METHODS: C57BL/6 female mice, fed a high-fat Paigen diet, were administered an oral dose of FABAC or DDH2O daily. Quantification of atherosclerotic fatty-streak lesions at the aortic sinus was performed. RESULTS: The FABAC-treated mice showed a significant reduction in the atherosclerotic lesion areas as compared to the control group (p = 0.019). A significant elevation in total cholesterol levels was observed in both the FABAC and control groups. Higher FABAC levels were measured in the high-density lipoprotein fraction as compared to the very-low-density and low-density lipoprotein fractions. CONCLUSION: Our findings demonstrate that FABACs, given orally, reduce the development of atherosclerosis in mice fed a high-fat high-cholesterol diet, despite a lack of effect on plasma lipid levels.     

Post-sigh breathing behavior and spontaneous pauses in the C57BL/6J (B6) mouse

The purpose was to examine sighs and spontaneous pauses in regard to the stability of resting breathing in the B6 strain, compared to the A/J strain. A 5-HT_1A receptor agonist (buspirone) and a chromosomal substitution strain (B6a1) were used to further alter breathing patterning. Ten-minute recordings of room air breathing were collected from unanaesthetized B6, A/J, and B6a1 mice. Despite no differences between strains in the magnitude and incidence of sighs, post-sigh apneas, the variation for duration of expiration (T_e) after sighs, and the number of spontaneous pauses were greater in the B6, while Shannon Entropy (nonlinear metrics) for T_e after sighs was lower in B6, compared to the other strains. Buspirone and chromosomal substitution eliminated post-sigh apneas and decreased spontaneous pauses. A greater irregularity and the lower complexity of post-sigh breathing in B6 are reversed by elements on A/J chromosome 1 and by increased 5-HT_1A serotonergic tone.     

The C57BL/6 nu/nu lpr/lpr mouse. I. Expression of the 'lpr phenotype' in the C57BL/6 genetic background

The C57BL/6 lpr/lpr mice develop within 3-6 moths a series of abnormalities of their immune system which characterize the 'lpr phenotype' and allow them to be distinguished easily from normal C57BL/6 as well as from C57BL/6 nu/nu: lymphadenopathy, hyperimmunoglobulinemia, high anti-nuclear antibody titers and, less regularly, anti-whole DNA antibody. Though C57BL/6 nu/nu occasionally present auto-antibody too, the combined use of three or four of the aforementioned parameters for each tested animal allows an easy detection of animals presenting the lpr phenotype. In our C57BL/6 lpr/lpr colony, the lymphadenopathy does not seem to start by chance in any lymphoid organ but shows a very strong preferential occurrence in the cervical lymph nodes. These parameters of the lpr phenotype have been used to trace the lpr genes and to construct the C57BL/6 nu/nu lpr/lpr as described in the companion paper.     

Slow disease progression in a C57BL/6 pten-deficient mouse model of prostate cancer

Prostate-specific deletion of Pten in mice has been reported to recapitulate histological progression of human prostate cancer. To improve on this model, we introduced the conditional ROSA26 luciferase reporter allele to monitor prostate cancer progression via bioluminescence imaging and extensively backcrossed mice onto the albino C57BL/6 genetic background to address variability in tumor kinetics and to enhance imaging sensitivity. Bioluminescence signal increased rapidly in Pten(p-/-) mice from 3 to 11 weeks, but was much slower from 11 to 52 weeks. Changes in bioluminescence signal were correlated with epithelial proliferation. Magnetic resonance imaging revealed progressive increases in prostate volume, which were attributed to excessive fluid retention in the anterior prostate and to expansion of the stroma. Development of invasive prostate cancer in 52-week-old Pten(p-/-) mice was rare, indicating that disease progression was slowed relative to that in previous reports. Tumors in these mice exhibited a spontaneous inflammatory phenotype and were rapidly infiltrated by myeloid-derived suppressor cells. Although Pten(p-/-) tumors responded to androgen withdrawal, they failed to exhibit relapsed growth for up to 1 year. Taken together, these data identify a mild prostate cancer phenotype in C57BL/6 prostate-specific Pten-deficient mice, reflecting effects of the C57BL/6 genetic background on cancer progression. This model provides a platform for noninvasive assessment of how genetic and environmental risk factors may affect disease progression.     

Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics

The development of the metabolic syndrome in an increasing percentage of the populations of Western societies, particularly in the United States, requires valid models for establishing basic biochemical changes and performing preclinical studies on potential drug targets. The C57BL/6J mouse has become an important model for understanding the interplay between genetic background and environmental challenges such as high-fat/high-calorie diets that predispose to the development of the metabolic syndrome. This review highlights metabolic and signal transduction features that are altered during the course of disease progression, many of which mirror the human situation.     

Prenatal behavior of the C57BL/6J mouse: a promising model for human fetal movement during early to mid-gestation

The study of fetal neurobehavioral development in genetically altered mice promises a significant advance in our understanding of the prenatal origins of developmental disabilities in humans. Despite their importance, little is known about fetal neurobehavioral development in mice. In this study, we observed prenatal behavioral patterns of the C57BL/6J mouse, a common background strain for genetically altered mice, and report their similarity to those observed in the early to mid-gestation human fetus. Fetal offspring from pregnant C57BL/6J dams were observed on the day before birth (E18 of a 19-day gestation). Scoring and analysis of fetal movement included Prechtl's Method for Qualitative Assessment, Interlimb Movement Synchrony, a measure of the temporal relationship between movements of limb pairs, and Behavioral State, quantified through detailed analysis of high and low amplitude limb movements. With the exception of fetal breathing movements, all categories and patterns of behavior typically reported in the early to mid-gestation human fetus were observed in the C57BL/6J mouse fetus. Our results suggest that behavioral analysis of fetal C57BL/6J mice may yield important new insights into early to mid-gestation human behavioral development.     

Genomic copy number and expression variation within the C57BL/6J inbred mouse strain

The C57BL/6J strain is one of the most widely used animal models for biomedical research, and individual mice within the strain are often assumed to be genetically identical after more than 70 yr of inbreeding. Using a single nucleotide polymorphism (SNP) genotyping panel, we assessed if copy number variations (CNVs) could be detected within the C57BL/6J strain by comparing relative allele frequencies in first generation (F(1)) progeny of C57BL/6J mice. Sequencing, quantitative PCR, breeding, and array comparative genomic hybridization (CGH) together confirmed the presence of two CNVs. Both CNVs span genes encoded on chromosome 19, and quantitative RT-PCR demonstrated that they result in altered expression of the insulin-degrading enzyme (Ide) and fibroblast growth factor binding protein 3 (Fgfbp3) genes. Analysis of 39 different C57BL/6J breeders revealed that 64% of mice from the Jackson Laboratory colony were heterozygous for the CNV spanning Ide. Homozygotes with and without the duplication were present in concordance with Hardy-Weinberg equilibrium (13% and 23%, respectively), and analysis of archived samples from the C57BL/6J colony suggests that the duplication has rapidly reached a high frequency in the colony since 1994. The identification of two CNVs in the small portion of the genome screened demonstrates that individual mice of highly inbred strains are not isogenic and suggests other CNVs may be segregating within C57BL/6J as well as other carefully maintained inbred strains. These differences can influence interpretations of physiological, biomedical, and behavioral experiments and can be exploited to model CNVs apparent in the human genome.     

Punta Toro virus infection of C57BL/6J mice: a model for phlebovirus-induced disease

Punta Toro virus infections of inbred strains of mice have been characterized and evaluated as a model in which to study various aspects of the host response to phlebovirus infections and the requirements for protective immunity. The Adames strain of Punta Toro virus was found to be strongly hepatotropic and lymphotropic and the outcome of infection was largely a function of age. C57BL/6J mice of less than 5 weeks of age uniformly developed fulminant hepatocellular necrosis with mean survival times of 4.2 days. Resistance to lethal infection increased with age such that greater than 95% of 8-week-old mice survived challenge. The kinetics of viremia, antibody production, and hematological changes in 4- and 8-week animals indicated that the survival of the older animals is related to their ability to delay virus replication and the development of hepatic lesions during the initial 48 h of infection and their ability to terminate virus replication and clear virus from the circulation 4 to 5 days after infection. The mechanisms responsible for this resistance were studied using anti-interferon serum, immunosuppression, and passive immunization.