Effect of caging singly or in groups of different sizes on the thermogenic activity of interscapular brown adipose tissue in mice

The effects on the thermogenic activity of brown adipose tissue of caging mice singly or in groups of different sizes has been investigated. At 23 degrees C the total cytochrome oxidase activity and the level of mitochondrial GDP binding were higher in mice caged singly than in mice caged in groups of three or six. At 4 degrees C GDP binding and cytochrome oxidase activity were lower in mice caged in groups of two, three or six than in mice caged singly. The mitochondrial concentration of uncoupling protein was not clearly affected by the number of mice in each cage.     

Aggressive behaviour in related and unrelated wild house mice (Mus musculus L.)

Aggressive behaviour was observed to be rare in small family groups of confined wild house mice, Mus musculus L. Unrelated mice were attacked when they were introduced to a family group and in their presence intra-family aggressive behaviour increased. When two family groups of mice were allowed to meet there were frequent aggressive encounters between unrelated animals and the two groups remained separate. Resident mice were found to be aggressive towards males and females individually isolated and returned to their own family after 2 or 3 weeks absence but not after 1 week. The possibility is discussed that in wild mice odour discrimination influences the dispersal and build-up of free-living populations.     

Energetics of mice in stable and unstable social conditions: Evidence of an air-borne factor affecting metabolism

The metabolic rates of laboratory mice were compared in three conditions: isolated mice, mice paired together over six days (stable groups), and mice paired with strange partners daily (unstable groups). Stable pairs had 15% lower metabolic rates than either isolated or unstable pairs. In other experiments when two mice were placed in separate metabolic chambers and connected together via an air flow, the metabolic rate of the recipient in the series was 35% lower than the donor. The data suggest that a ‘factor’ produced by the donor mouse was passed via the air supply into the recipient's chamber.     

表达人肝再生增强因子肝细胞系生物人工肝治疗安全性的动物实验初步研究

目的：评价表达人肝再生增强因子基因的HepG2细胞系的细胞培养上清及细胞裂解物的小鼠急性毒性和近期致瘤性。方法：SPF级昆明种小鼠18只,随机分为空白对照组、细胞培养上清组、细胞裂解物组,每组小鼠各6只,腹腔分别接种空白培养液、细胞培养上清、细胞裂解物0．5ml。连续14天,每天观察记录动物毒性反应,14d后宰杀小鼠,取血测血生化指标。及观察病理改变。结果：各组小鼠均存活。除对照组1例小鼠,细胞培养上清组1例小鼠,细胞裂解物组2例小鼠次日活动稍减少外,均未见异常反应。血液生化检测ALT、AST、AFP、TBIL无明显异常,且各组间无差别。普通光镜下各组动物肝脏病理切片染色均未见明显异常。结论：目的细胞系细胞培养上清、细胞裂解物对实验用昆明小鼠无明确毒副作用及短期致瘤性。可能提供一种安全的可用于生物人工肝新的细胞来源。     

表达人肝再生增强因子肝细胞系生物人工肝治疗安全性 的动物实验初步研究

目的:评价表达人肝再生增强因子基因的HepG2细胞系的细胞培养上清及细胞裂解物的小鼠急性毒性和近期致瘤性。方法:SPF级昆明种小鼠18只,随机分为空白对照组、细胞培养上清组、细胞裂解物组,每组小鼠各6只,腹腔分别接种空白培养液、细胞培养上清、细胞裂解物0.5ml。连续14天,每天观察记录动物毒性反应,14d后宰杀小鼠,取血测血生化指标,及观察病理改变。结果:各组小鼠均存活。除对照组1例小鼠,细胞培养上清组1例小鼠,细胞裂解物组2例小鼠次日活动稍减少外,均未见异常反应。血液生化检测ALT、AST、AFP、TBIL无明显异常,且各组间无差别。普通光镜下各组动物肝脏病理切片染色均未见明显异常。结论:目的细胞系细胞培养上清、细胞裂解物对实验用昆明小鼠无明确毒副作用及短期致瘤性,可能提供一种安全的可用于生物人工肝新的细胞来源。     

Use of the MHC for mate choice in wild house mice (Mus domesticus)

The mechanisms maintaining natural diversity at the major histocompatibility complex (MHC) are not well understood. To increase knowledge of one potential mechanism, I examined the use of MHC genes for mate choice by wild house mice in a controlled laboratory setting. Three rearing groups of wild test mice were produced: non‐fostered control mice, mice fostered into families of an inbred laboratory mouse strain, and mice fostered into families of a second, MHC‐congenic mouse strain. Mature test mice were given a choice of two opposite‐sex stimulus mice from the two MHC‐congenic strains used for fostering, and were scored for several measures of preference. The results were non‐significant in general, but females of two rearing groups spent significantly more time with mice of one MHC‐type, and in most rearing groups, mice tended to spend more time with this same MHC‐type. Other results showed that male test mice ejaculated indiscriminantly and that female wild mice mated to ejaculation more often in longer length trials, but showed no significant preferences. In this study, fostering seemed to have little or no effect on MHC‐based mate preferences of wild house mice, and wild mice did not appear to be using the MHC to avoid inbreeding. However, some wild female mice used the MHC to choose potential mates. This revised version was published online in July 2006 with corrections to the Cover Date.     

抗VEGFR-2嵌合Fab抗体对裸鼠肝癌原位移植瘤新生血管生成的影响

目的:检测抗VEGFR-2嵌合Fab抗体对裸鼠肝癌原位移植瘤血管生成的影响.方法:建立裸鼠肝癌H22细胞原位移植瘤模型,随机分成生理盐水组(n=12)和抗体组(n=12).采用免疫组织化学SP染色法对两组肝脏移植瘤进行血管染色,观察其微血管密度(MVD)情况.结果:成功建立裸鼠H22肝癌原位移植瘤模型,HE染色显示肝脏移植瘤为肝细胞肝癌,免疫组化结果显示肝脏实体瘤内微血管密度抗体组较生理盐水组显著性减少(25.64± 1.53 vs 8.65± 1.79,P＜0.05).结论:抗VEGFR-2嵌合Fab抗体能够抑制裸鼠肝癌原位移植瘤的血管生成.     

Effects of Aspiculuris tetraptera dn Syphacia obvelata on exploratory behavior of an inbred mouse strain

Sixty C57BL/6 male mice were treated with an anthelmintic for 2 weeks to free them of pinworms. They were then divided into six groups. Two groups were infected with Aspiculuris tetraptera, two groups with Syphacia obvelata, and two groups were left uninfected as controls. At intervals of 2 and 4 weeks after infection, the mice were tested for exploratory activity in a barriered field apparatus. Following the second test, each mouse was necropsied to determine presence of nematodes and to estimate worm burdens. Statistical analysis showed significant depression of exploratory activity in mice harboring S obvelata. No significant depression was found in those harboring A tetraptera.     

Influence of hindlimb suspension on calcium-induced contraction characteristics in dystrophin-deficient animals

The direct data concerning effects of unloading on dystrophic muscle were received in study of mdx mice, a model for Duchenne muscular dystrophy, muscles before and after hindlimb suspension. Experiments were performed on softer skinned soleus muscle fibers isolated from wild-type (C57black) as a control and mdx mice aged 2 weeks. Animals of two experimental groups were tail suspended during 21 days. In both groups of hindlimb suspended mice isolated soleus fibers were thinner than in the control groups. But there was a greater 37% significant decrease in fiber diameter in wild-type (CHS) suspended mice vs. 24% in mdx (MHS) suspended group. Values of absolute peak tension in CHS were less than in the control group by 33%, and in MHS mice suspended--by 39%. 21 days of hindlimb suspension resulted in reduction of mean peak specific tension by 28% in MHS and significantly less drop (15%) in CHS groups. We observed a similar rightward shift of the tension pCa curve in both mice strains.     

Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse

To determine the importance of IL-6 in acetaminophen (APAP) toxicity, wild type (WT) and IL-6 knock out (KO) mice were dosed with APAP (300 mg/kg i.p.) and sacrificed at 4 and 24h. No differences were found between the two groups by analysis of serum AST levels or histopathology. Also, the relative amounts of APAP protein binding and nitrotyrosine formation were equal. Subsequently, WT and KO mice were dosed with APAP (300 mg/kg i.p.) and sacrificed at 24, 48, and 72 h. AST normalized by 48 h in the WT mice, but not until 72 h in the KO mice. The severity of the histopathological alterations was comparable in the two groups of mice; however, fewer regenerating hepatocytes were present in the KO mice. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) showed reduced staining in the KO mice. Pretreatment of KO mice with IL-6 lowered AST and normalized PCNA staining in the IL-6 KO mice. These data suggest that IL-6 is important in hepatocyte regeneration following APAP toxicity in the mouse.     

苦瓜皂甙对衰老动物内分泌功能的影响

目的 :探讨苦瓜皂甙对衰老动物内分泌功能的调节作用。方法 :15月龄雌性老年昆明小鼠 ,随机分为老年对照组、实验 1组和实验 2组三组 ,同时准备 4月龄雌性昆明小鼠作青年对照组 ,其中两对照组饮水为普通水 ,两个实验组饮水分别含有 10 0mg/L及 2 0 0mg/L苦瓜皂甙 ,饲养 5周后取血清标本待测。同时 ,取 12月龄大鼠胸腺细胞培养 ,检测不同浓度苦瓜皂甙对雌激素受体蛋白表达的影响。结果 :与青年对照组相比 ,衰老小鼠血清ACTH、雌二醇水平显著降低。与老年对照组相比 ,两实验组血清雌二醇水平均明显升高 ,ACTH水平有升高趋势 ,但只有高剂量组有显著性 ;两组之间所有指标均没有显著性差异。体外实验发现 ,苦瓜皂甙明显促进雌激素受体蛋白的表达 ,却不影响其mRNA水平。结论 :苦瓜皂甙可通过调节ACTH分泌及雌激素受体表达来改善衰老机体内分泌功能     

Enhanced baroreflex sensitivity in free-moving calponin knockout mice

Calponin is an actin binding protein in vascular smooth muscle that modifies contractile responses. However, its role in mean arterial pressure (MAP) regulation has not been clarified. To assess this, MAP and heart rate (HR) were measured in calponin knockout (KO) mice, and the results were compared with those in wild-type (WT) mice. The measurements were performed every 100 ms during a 60-min free-moving state each day for 3 days. Mice in both groups rested during approximately 70% of the total measuring period. The mean HR during rest was significantly lower in KO mice than in WT mice but with no significant difference in MAP between the groups. The change in HR response (deltaHR) to spontaneous change in MAP (deltaMAP) varied in a wider range in KO mice with an 80% increase in the coefficient of variation for HR (P < 0.05), whereas MAP in KO mice was controlled in a narrow range similar to that in WT mice. The baroreflex sensitivity (deltaHR/deltaMAP), determined from the change in HR to the spontaneous change in MAP, was twofold higher in KO mice than that in WT mice (P < 0.01), whereas there were no significant differences in the baroreflex sensitivity determined by intravascular administration of phenylephrine and sodium nitroprusside between the two groups (P > 0.1). The MAP response to the administrated doses of phenylephrine in KO mice was reduced to one-half of that in WT mice (P < 0.01) but with no significant difference in the response to sodium nitroprusside between the groups. The differences in HR variability and the spontaneous baroreflex sensitivity between the two groups completely disappeared after carotid sinus denervation. These results suggest that the higher variability in HR for KO mice was caused by the increased spontaneous arterial baroreflex sensitivity, though not detected by the intra-arterial administration of the drug, and that the higher variability of HR may be a compensatory adaptation to the blunted alpha-adrenergic response of peripheral vessels to sympathetic nervous activity.     

Basal metabolic rate and lipid and liver glycogen in mice infected by the nematode Nematospiroides dubius

The basal metabolic rate (BMR) of mice losing weight about two weeks after infection by Nematospiroides dubius was lower than that of uninfected mice gaining weight when fed ad libitum or losing weight on quantitatively reduced rations. There was no difference in BMR between the latter two groups.Following the injection of ¹⁴C-glucose, the high specific activity of expired CO₂ from infected and reduced ration mice was considered to be due to the utilization of energy reserves. The levels of lipid and liver glycogen were low in these two groups of mice and their specific activities, particularly in the severely affected animals, were high.It was concluded that the depressed BMR of infected mice is unrelated to anorexia, which did, however, explain the low levels of lipid and liver glycogen.     

番石榴多糖对糖尿病小鼠的血糖及胸腺、脾指数的影响

研究采用两种不同方法提取的番石榴多糖对四氧嘧啶致糖尿病的小鼠血糖值及胸腺、脾指数的影响。通过给小鼠腹腔注射四氧嘧啶(200 mg/kg BW)建立糖尿病小鼠模型,尾端取血,采用血糖仪分别在给小鼠灌胃多糖三天和十天后检测小鼠血糖值,第十天解剖小鼠,分别对小鼠胸腺和脾脏称重。结果表明:与糖尿病对照组比较,两组灌喂番石榴多糖的小鼠的生存质量提高,血糖值显著降低,同时胸腺指数显著增加,提示番石榴多糖具有降血糖作用,是一种潜在的糖尿病治疗药物。     

IL-10在输血相关性移植物抗宿主病小鼠模型中的免疫调节作用

目的:IL-10在输血相关性移植物抗宿主病小鼠模型中的免疫调节作用。方法:取BALB/c实验小鼠免疫活性淋巴细胞,分别输注于BALB/c小鼠(设为A组)及BALB/c裸鼠(设为B组),建立TA-GVHD模型,观察小鼠症状,HE染色判断小鼠肝、肺、小肠、皮肤病理变化情况;采用双夹心酶联免疫吸附法(ELISA)检测两组小鼠血清IL-10浓度;用逆转录聚合酶链反应法RT-PCR检测移植后外周血单个核细胞中IL-10的表达。结果:A组中2只死亡(12.5%),B组中3只死亡(18.75%),共5只死亡,29只存活,两组死亡率比较无明显差异(P>0.05)。B组小鼠累及肝、肺、小肠和皮肤病理损伤程度较A组严重;存活小鼠IL-10浓度较死亡小鼠明显升高(P2<0.05);存活小鼠IL-10 mRNA表达阳性率96.55%明显高于死亡小鼠(20.00%)。结论:IL-10在输血相关的移植物抗宿主病小鼠模型中发挥负向免疫调节--免疫抑制作用。     

Antioxidant mechanisms in apolipoprotein E deficient mice prior to and following closed head injury

Apolipoprotein E deficient mice have distinct memory deficits and neurochemical derangements and their recovery from closed head injury is impaired. In the present study, we examined the possibility that the neuronal derangements of apolipoprotein E deficient mice are associated with oxidative stress, which in turn affects their ability to recover from close head injury. It was found that brain phospholipid levels in apolipoprotein E deficient mice are lower than those of the controls (55+/-15% of control, P<0. 01), that the cholesterol levels of the two mice groups are similar and that the levels of conjugated dienes of the apolipoprotein E deficient mice are higher than those of control mice (132+/-15% of P<0.01). Brains of apolipoprotein E deficient mice had higher Mn-superoxide dismutase (134+/-7%), catalase (122+/-8%) and glutathione reductase (167+/-7%) activities than control (P<0.01), whereas glutathione peroxidase activity and the levels of reduced glutathione and ascorbic acid were similar in the two mouse groups. Closed head injury increased catalase and glutathione peroxidase activities in both mouse groups, whereas glutathione reductase increased only in control mice. The superoxide dismutase activity was unaffected in both groups. These findings suggest that the antioxidative metabolism of apolipoprotein E deficient mice is altered both prior to and following head injury and that antioxidative mechanisms may play a role in mediating the neuronal maintenance and repair derangements of the apolipoprotein E deficient mice.     

Antitumor activity of two BCG vaccine preparations against the lewis lung carcinoma in mice

Summary Two BCG vaccine preparations were prepared following different production methods. Immuno-BCG Pasteur F was produced by surface culture on Sauton medium; BCG-RIV was a homogenous stirred deep culture.The antitumor effects of the two BCG vaccines were investigated on the Lewis lung carcinoma (3LL) in C57Bl/6 mice. A direct relationship exists in this tumor model between the log₁₀ dose of single-cell suspension inoculated subcutaneously in the hind footpad of mice and the onset and the degree of local tumor growth and the time of death, which is directly related to the lung metastases. No significant difference from control mice was observed in the two groups of BCG-immunized mice when 3LL tumor cells were injected 2 weeks after BCG immunization. When varying numbers of viable units of the two BCG vaccines were injected together with 10⁵ tumor cells in separate groups of normal mice, a dose-dependent local reaction was observed with Immuno-BCG Pasteur F, which was associated with a delay in the onset and development of tumor growth and an increase in the mean survival time. The local inflammatory reaction produced with BCG-RIV was of lower magnitude, and only the highest concentration (1.8×10⁶ viable units) led to some delay in tumor occurrence and mortality. The antitumor effect of a specific local delayed-type hypersensitivity (DTH) elicited by varying amounts of the two BCG preparations injected together with 10⁵ tumor cells in separate groups of normal or BCG-immunized mice showed that the challenge injection of Immuno-BCG Pasteur F was in all cases more effective than the BCG-RIV, but these two vaccines were more effective in BCG-RIV-immunized mice than in Immuno-BCG F Pasteur-immunized mice.When the same number of viable units within each BCG vaccine was used as a criterion of comparison, Immuno-BCG Pasteur F produced a higher specific and nonspecific local inflammatory reaction (which was associated with a local antitumor effect) than BCG-RIV. But within 2 weeks, the latter was much better able to sensitize the mice to mycobacterial antigens. This was confirmed by the evaluation of local granuloma formation and tuberculin hypersensitivity. BCG vaccines prepared as surface-grown pellets and mechanically dispersed always sensitized mice to a lesser degree and after a much longer period of time than did the well-dispersed deep-cultured vaccine.     

Stimulation of glutathione synthesis in iron-loaded mice

We have previously reported that the iron-loading of mice, by feeding them carbonyl iron, caused an elevation of hepatic glutathione concentration and an increase in glutathione excretion from the liver (Kawabata, T., Ogino, T. and Awai, M. (1989) Biochim. Biophys. Acta 1004, 89-94). To elucidate the mechanism of glutathione elevation, hepatic cysteine concentration and gamma-glutamylcysteine synthetase (L-glutamate: L-cysteine gamma-ligase (ADP-forming), EC 6.3.2.2) activity were measured and possible changes in cysteine metabolism were also compared between iron-loaded and control mice. Hepatic cysteine concentration was higher in iron-loaded mice (185 +/- 12 nmol/g wet wt.) than in the controls (164 +/- 8 nmol/g wet wt.), and gamma-glutamylcysteine synthetase activity was also elevated in iron-loaded mice (34.3 +/- 3.2 nmol/mg protein per min) compared with the controls (28.6 +/- 3.8 nmol/mg protein per min). A comparison of the metabolic pathways with intravenously injected [35S]cysteine showed that organ distribution of the isotope was not significantly different, and also the rate of [35S]cysteine uptake into the hepatic glutathione fraction exhibited no difference between the two groups of mice. This shows that hepatic cysteine turnover may not be different between the two groups of mice. Since hepatic cysteine concentration was higher in iron-loaded mice, the apparently equal turnover of hepatic cysteine suggests that GSH synthesis may be elevated in iron-loaded mice. The high gamma-glutamylcysteine synthetase activity is suggested to stimulate GSH synthesis in iron-loaded mice.     

Liver-derived IGF-I contributes to GH-dependent increases in lean mass and bone mineral density in mice with comparable levels of circulating GH

The relative contributions of circulating and locally produced IGF-I in growth remain controversial. The majority of circulating IGF-I is produced by the liver, and numerous mouse models have been developed to study the endocrine actions of IGF-I. A common drawback to these models is that the elimination of circulating IGF-I disrupts a negative feedback pathway, resulting in unregulated GH secretion. We generated a mouse with near total abrogation of circulating IGF-I by disrupting the GH signaling mediator, Janus kinase (JAK)2, in hepatocytes. We then crossed these mice, termed JAK2L, to GH-deficient little mice (Lit). Compound mutant (Lit-JAK2L) and control (Lit-Con) mice were treated with equal amounts of GH such that the only difference between the two groups was hepatic GH signaling. Both groups gained weight in response to GH but there was a reduction in the final weight of GH-treated Lit-JAK2L vs. Lit-Con mice. Similarly, lean mass increased in both groups, but there was a reduction in the final lean mass of Lit-JAK2L vs. Lit-Con mice. There was an equivalent increase in skeletal length in response to GH in Lit-Con and Lit-JAK2L mice. There was an increase in bone mineral density (BMD) in both groups, but Lit-JAK2L had lower BMD than Lit-Con mice. In addition, GH-mediated increases in spleen and kidney mass were absent in Lit-JAK2L mice. Taken together, hepatic GH-dependent production of IGF-I had a significant and nonredundant role in GH-mediated acquisition of lean mass, BMD, spleen mass, and kidney mass; however, skeletal length was dependent upon or compensated for by locally produced IGF-I.     

MLD-STZ诱导1型糖尿病小鼠胰腺比较蛋白质组学研究

目的：通过对小剂量多次链脲佐菌素（multiple low doses of streptozotocin MLD-STZ）诱导的1型糖尿病模型小鼠胰腺与正常小鼠胰腺蛋白的比较分析,拟从蛋白水平上对1型糖尿病发病机制进行探讨。方法：将20只雄性昆明鼠,按体重随机分为MLD-STE模型组和正常对照组（n=10）,应用二维凝胶电泳技术获得胰腺的二维电泳图谱,经ImageMaster2D 5．0软件分析获得差异蛋白,结合质谱（MALDI-TOF-MS）与MASCOT网络数据库进行匹配鉴定蛋白。结果：与正常对照组比较,模型组胰腺中有23个蛋白表达改变,其中15个蛋白表达下调,8个蛋白表达上调。经肽质量指纹图谱分析及蛋白数据库检索,最终鉴定出15个差异蛋白,根据其功能可分为：①代谢相关蛋白;②氧化应激相关蛋白;③催化酶类;④细胞骨架蛋白;⑤伴侣蛋白;⑥免疫相关蛋白;⑦其他蛋白。结论：研究结果表明模型组胰腺蛋白表达存在明显改变,提示1型糖尿病的发生是多途径多靶点的共同作用,同时这些改变蛋白为研究和治疗糖尿病等相关疾病提供了新靶标。