三种品系小鼠对伴刀豆球蛋白A所致急性肝损伤的耐受性比较研究

目的：应用不同剂量伴刀豆球蛋白 A（ConA）诱导三种不同品系小鼠急性肝损伤,比较肝酶变化、死亡率和肝组织病理学变化。方法分别用6、12、20和30 mg·kg-1 ConA 处理 C57BL/6J、BABL/c 和 KM 小鼠,8 h 后对比观察急性肝损伤动物血清酶学及肝组织病理学变化情况。结果在6 mg·kg-1 ConA 的作用下,三个品系小鼠均被成功制造出急性肝损伤模型;在12 mg·kg-1 ConA 作用下,KM 小鼠血清 ALT 和AST 分别为（1006.8±12.1） U/L 和（1391.8±13.4）U/L,显著高于 BABL/c 小鼠[（75.7±0.5）U/L 和（284.7±23.4） U/L）和 C57BL/6J 小鼠（104.4±32.2）U/L 和（492.2±12.3）U/L,P 均〈0.05];同样,KM 小鼠肝指数和脾指数分别为（5.4±0.3）和（0.7±0.5）,均显著高于 BABL/c 小鼠[（5.2±0.4）和（0.6±0.3）和 C57BL/6J 小鼠（5.0±0.6）和（0.6±0.2）,P 均〈0.05];在20 mg·kg-1 ConA 作用下,三组小鼠血清 AST 和 ALT 水平无统计学差异,但 BABL/c 小鼠（4/10）和 C57BL/6J 小鼠（5/10）死亡率显著高于 KM 小鼠（1/10）;在30 mg·kg-1 ConA 作用下,三个品系小鼠死亡率均较高（KM 小鼠为30%,BABL/c 和C57BL/6J 小鼠均为100%）。结论不同品系的小鼠对 ConA 的耐受性不同,KM 小鼠对 ConA 的耐受性明显优于BABL/c 小鼠和 C57BL/6J 小鼠,且呈剂量依赖性。     

Protective immunity to Schistosoma japonicum infection depends on the balance of T helper cytokine responses in mice vaccinated with gamma-irradiated cercariae

Although the strain difference in protection of mice to Schistosoma mansoni infection has been described, limited information is available in the case of Schistosoma japonicum. In the present study, we compared the protective immunity to S. japonicum infection and cytokine production in various strains of mice vaccinated with gamma-irradiated cercariae. A significant reduction in worm recovery was observed in male and female mice of DBA/2 at a 6-week interval between vaccination and a challenge infection, whereas vaccinated mice of C57BL/6, C57BL/10, (C57BL/6 x DBA/2) F1 (B6D2F1) and (C57BL/10 x DBA/2) F1 (B10D2F1) showed no detectable level of protection. No sex-linked difference in development of resistance was observed in any of the strains so far examined. Vaccination with gamma-irradiated cercariae twice with a 3-week interval also induced significant protection against a challenge infection in DBA/2 but not in BALB/c or C57BL/6 strains. Further studies demonstrated that spleen cells of vaccinated C57BL/6 mice produced lower levels of IFN-gamma compared to the cells of vaccinated BALB/c and DBA/2. On the other hand, production of IL-10 by spleen cells was relatively higher in BALB/c mice than in the other two strains. Macrophages that had been stimulated with spleen cell culture supernatants derived from vaccinated DBA/2 damaged schistosomula more effectively than cells stimulated with supernatants derived from the other strains. These results suggest that different levels of protection observed among strains of mice depend on the balance of cytokine responses which consequently activate or suppress macrophage-mediated damage to schistosomula.     

自然调节性T细胞对脑型疟疾易感鼠和抵抗鼠感染结局的影响

目的探讨自然调节性T细胞(nTregs)在伯氏疟原虫感染过程中的活化特点及其与疾病进展的相关性。方法用伯氏疟原虫ANKA分别感染C57BL/6、BALB/c和DBA/2小鼠,计数红细胞感染率;感染前和感染后3、5、8d制备脾细胞悬液,流式细胞术检测脾细胞悬液中nTregs百分含量;ELISA和Griess方法检测脾细胞培养上清IFN-γ、IL-10和NO水平。结果C57BL/6小鼠感染后8～11d死于脑疟,BALB/c和DBA/2小鼠感染后3～4w死于贫血和过度虫体血症。3种小鼠于感染后3d,nTregs百分数达到峰值后逐渐下降,于感染后8d,C57BL/6小鼠nTregs百分数下降最为显著并明显低于正常水平,整个感染过程中,C57BL/6小鼠的nTregs百分含量显著低于BALB/c和DBA/2小鼠。3种小鼠脾细胞培养上清IFN-γ、NO和IL-10水平于感染后开始升高,感染后5d达到峰值,感染后8d与感染后5d相比,C57BL/6小鼠IFN-γ、NO水平轻微下降,IL-10水平显著下降;BALB/c和DBA/2小鼠IFN-γ、NO水平显著下降,IL-10水平轻微下降。并且C57BL/6小鼠IFN-γ、NO水平高于BALB/c和DBA/2小鼠,而IL-10水平低于BALB/c和DBA/2小鼠。3种小鼠感染后脾脏nTregs数量与IFN-γ和NO水平呈负相关,IL-10水平与感染率呈正相关。结论伯氏疟原虫感染过程中,nTregs数量的动态变化与宿主感染结局密切相关。     

Effects of anticonvulsant agents on halothane-induced liver injury in human subjects and experimental animals

In order to evaluate the clinical implication of experimental studies on halothane-induced liver damage in phenobarbital-treated rats, we studied the clinical records of 315 consecutive patients who underwent brain surgery with halothane anesthesia. After exclusion of subjects with a history of alcoholism or antecedent chronic liver disease, clinical data of 279 patients with normal preoperative transaminase activities were analyzed. The incidence of halothane-induced liver injury was significantly higher in the subjects given phenobarbital than in those with no phenobarbital medication (7/100 vs. 1/179, p less than 0.01). To determine if other anticonvulsant compounds can influence halothane-induced liver injury, rats were pretreated with diphenylhydantoin or valproic acid prior to exposure to halothane under hypoxic conditions for comparison with phenobarbital. The degree of halothane hepatotoxicity assessed from ALT activities and morphological alterations was of the decreasing order of phenobarbital greater than controls = diphenylhydantoin greater than valproic acid, and a similar order was observed in the extent of reductive metabolism of halothane. These results indicate that patients pretreated with phenobarbital may be at a greater risk of halothane-induced liver damage, and that treatment with valproic acid and diphenylhydantoin lead to the production of toxic intermediates of halothane to a lesser extent than treatment with phenobarbital does.     

NS-1 (Nervous System Antigen-1), a Glial-Cell-Specific Antigenic Component of the Surface Membrane

A methylcholanthrene-induced glioblastoma of the C57BL/6 inbred mouse strain was used to raise antibodies in C57BL/6 and C57BL/10 inbred mice and in (C57BL/6 x DBA/2) and (C57BL/6 x Balb/c) F(1) hybrids. When examined by the cytotoxicity test, these antibodies define a cell-surface component (or components) found exclusively on brain tissue of all mouse strains studied and of several other mammalian species including man. The antigen, named NS-1 (nervous system antigen-1), is present on cells of three of the four mouse-glial-cell tumors tested, but not on the C1300 neuroblastoma, a tumor of neuronal origin. NS-1 occurs in higher concentration in regions of the nervous system richer in white than in gray matter, and in lower than normal concentrations in brains of myelindeficient neurological mutant mice. The concentration of NS-1 gradually increases postnatally and reaches the adult level between the third and fourth week. The existence of more than one allele or genetic locus controlling NS-1 activity is suggested by the occurrence of higher amounts of NS-1 in brains of the A and C57BL/6 than of the Balb/c and DBA/2 mouse strains. NS-1 is the first cellsurface component to be described that is not only unique to nervous tissue, but specific for glial cells.     

AKT Network of Genes and Impaired Myocardial Contractility During Murine Acute Chagasic Myocarditis

Chagasic disease is associated with high morbidity in Latin America. Acute Chagasic myocarditis is consistently found in acute infections, but little is known about its contribution to chronic cardiomyopathy. The aim of the study was to phenotypically characterize two strains of mice with differential Chagas infection susceptibility and correlate strain myocarditis phenotypes with heart tissue gene expression. C57BL/6J and Balb/c mice were injected intraperitoneally with 0 or 150–200 tissue-derived trypomastigotes (Tulahuen strain). Echocardiograms, brain natriuretic peptide, and troponin were measured. Heart tissue was harvested for histopathological analysis and gene expression profiling on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J mice were identified. Echocardiograms showed differences in Balb/c versus C57BL/6J infected mice in heart rate (413 versus 476 beats per minute; P = 0.0001), stroke volume (31.9 ± 9.3 versus 39.2 ± 5.5 μL; P = 0.03), and cardiac output (13.1 ± 3.5 versus 18.7 ± 3.2 μL/min; P = 0.002). Gene expression at 4 weeks analysis showed 32 statistically significant (q value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J mice that were enriched for genes related to the protein kinase B (AKT) pathway. These specific phenotypic features of cardiac response during acute Chagasic myocarditis may, in part, be related to host AKT network regulation.     

Hürthle cells predict hypothyroidism in interferon-γ transgenic mice of different genetic backgrounds

Hürthle cells have long been described in Hashimoto thyroiditis but remain of undetermined significance. We have previously shown that Hürthle cells and hypothyroidism develop in C57BL/6J mice expressing interferon-γ (IFNγ) in the thyroid. To assess the influence of genetic backgrounds on Hürthle cell development, we crossed C57BL/6J IFNγ transgenic mice to 14 strains and analyzed thyroid histopathology and function in a cohort of 389 mice (225 transgenic and 164 wild type) using a multiple linear regression model that also included strain, sex, genotype, and major histocompatibility complex haplotype. We then queried the Johns Hopkins surgical pathology electronic archive for "Hashimoto" and/or "thyroiditis" keywords, reviewed the reports, and reexamined the Hashimoto slides. Hürthle cells were markedly affected by the genetic background: they were prominent and associated with hypothyroidism in the C57BL/6J, C57BL/6ByJ, C57BL/10J, C57BLKS/J, C57L/J, C58/J, and BPN/3J IFNγ transgenic strains, whereas they are mild or absent in the BPH/2J, BPL/1J, LP/J, CBA/J, Balb/cJ, DBA/1J, and NOD/ShiLtJ strains. Hürthle cells were the strongest predictor of hypothyroidism after adjusting for all the other covariates in the regression model. Interestingly, transgenic mice of the BPL/1J, DBA/1J, and NOD/ShiLtJ strains developed a marked accumulation of intrathyroidal brown adipocytes that was significantly associated with improved thyroid function. Hürthle cells were mentioned in 23% of the Hashimoto reports but increased to 79% upon our slide review. This study reports a novel association of Hürhtle cells and brown adipocytes on thyroid function that should prompt a reconsideration of their significance and role in pathogenesis of autoimmune thyroiditis.     

Encephalomyocarditis virus myocarditis in inbred strains of mice--chronic stage

Inbred strains of A/J, BALB/c, C3H/He, C57BL/6 and DBA/2 mice were inoculated with the M variant of encephalomyocarditis virus having a titer of 100 TCID50/0.1 ml. Myocardial lesions were seen in 73 of 150 BALB/c mice (48.7%), 160 of 259 C3H/He mice (61.8%) and 115 of 174 DBA/2 mice (66.1%). No pathologic findings were noted in A/J and C57BL/6 mice. In C3H/He and DBA/2 mice, dilatation and hypertrophy of the heart accompanying myocardial lesions persisted up to the 8th month after virus inoculation. The present study revealed that myocardial lesions similar to those in congestive (dilated) cardiomyopathy persisted for a long period after viral infection.     

Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice differ in sensitivity to ethanol excitation

BACKGROUND: The mesolimbic dopamine pathway that originates in the ventral tegmental area (VTA) is important for the rewarding effects of ethanol. Ethanol has been shown to excite dopaminergic neurons of the VTA, both in vivo and in vitro, in rats. Behavioral differences in the rewarding effects of ethanol have been observed between C57BL/6J and DBA/2J mice. The present electrophysiological study examined the effect of ethanol on individual dopaminergic VTA neurons from these two inbred mouse strains. METHODS: Extracellular single unit recordings of spontaneous action potentials were made from dopaminergic VTA neurons in brain slices from either C57BL/6J or DBA/2J mice. Ethanol (10 to 160 mM) was administered in the superfusate and the mean change in firing rate produced by ethanol was measured. RESULTS: There was no significant difference in basal spontaneous firing rate of dopaminergic VTA neurons between these two mouse strains. Ethanol caused a concentration-dependent increase in the firing rate of neurons from both mouse strains. Ethanol excited dopaminergic VTA neurons from DBA/2J mice more potently than those from C57BL/6J mice. CONCLUSIONS: The difference in sensitivity to ethanol excitation of dopaminergic VTA neurons in C57BL/6J and DBA/2J mice may contribute to differences in their behavioral response to ethanol. The fact that a given concentration of ethanol causes greater excitation of dopaminergic VTA (reward) neurons in DBA/2J mice than in C57BL/6J mice could explain why DBA/2J mice show much stronger place preference conditioning with ethanol. The higher voluntary intake of ethanol by C57BL/6J mice may be partly due to the insensitivity of their dopaminergic VTA neurons that requires them to drink a lot of ethanol to achieve sufficient excitation of reward neurons, whereas DBA/2J mice avoid oral ingestion of ethanol, despite its rewarding effect, because of their aversion to its taste.     

A spleen is not necessary to resolve infections with Plasmodium yoelii

The role of the spleen in resistance to infections with nonlethal Plasmodium yoelii 17x is dependent upon the genotype of the host. Thus, DBA/2 (D2) mice infected with P. yoelii 17x were not adversely affected by removal of the spleen, while splenectomized C57BL/6 (B6) or Balb/c mice failed to resolve their infections and eventually died. The levels of parasitemia were lower in splenectomized mice compared to intact controls; however, splenectomized mice became as anemic as did spleen-intact controls. Splenectomy resulted in the appearance of large aggregates of mononuclear cells in the livers of infected mice and also altered the liver/body weight ratios. These results indicate that D2 mice have a spleen-independent mechanism of clearing parasites which is lacking in B6 and Balb/c mice.     

Circulating factors may be responsible for murine strain-specific responses to mobilizing cytokines

OBJECTIVE: To determine if circulating factors influence strain-specific responses to administration of hematopoietic stem-cell mobilizing cytokines, a murine model was employed. METHODS: Plasma aliquots from intact DBA2, Balb/c, and C57Bl/6 mice were injected into intact Balb/c mice prior to delivery of mobilizing cytokines. Control Balb/c mice were injected with mobilizing cytokines alone. Plasma from hemi-body irradiated Balb/c mice, known to inhibit mobilization, was also injected into Balb/c mice. Twenty-four hours later, spleen cells were harvested and assayed for granulocyte-macrophage colony-forming cells (GM-CFC) and high-proliferative-potential colony-forming cells (HPP-CFC). Simultaneously harvested blood aliquots were assayed for CD45(+)/CD34(+) cells using flow cytometric techniques. RESULTS: Mice receiving plasma from any source demonstrated significant inhibition of mobilization of HPP-CFC and GM-CFC to the spleen as compared to mobilized controls; for HPP-CFC, plasma from C57Bl/6 mice was more inhibitory than plasma from Balb/c (p = 0.001) or from DBA2 mice (p = 0.01), while for GM-CFC, plasma from C57Bl/6 mice was more inhibitory than Balb/c plasma but not more inhibitory than DBA2 plasma. Mice injected with plasma from previously irradiated Balb/c mice exhibited the expected HPP-CFC and GM-CFC mobilization inhibition, which was not statistically different from the inhibition seen in animals that received C57Bl/6 plasma. Mobilization of CD34(+)/CD45(+) cells to the blood also appeared to be inhibited by pretreatment with C57Bl/6 plasma, but not DBA2 plasma. CONCLUSION: These data suggest that strain-specific patterns of mobilization may be influenced by a circulating mobilization inhibitor(s).     

Immunoglobulin isotypes and functional anti‐FVIII antibodies in response to FVIII treatment in Balb/c and C57BL/6 haemophilia A mice

Summary. Previous studies have demonstrated that genetic factors play an important role in determining the likelihood of formation of anti‐factor VIII (FVIII) antibodies in haemophilia A patients. We were interested in characterizing the spectrum of FVIII antibody formation and the primary and secondary immune responses after FVIII administration in two different exon 16‐disrupted haemophilia A mouse strains, Balb/c and C57BL/6. Balb/c and C57BL/6 E16 haemophilia A mice were used in all experiments. Total FVIII antibodies and FVIII inhibitors were measured using ELISA and Bethesda assays respectively. T‐ and B‐cell cytokines were quantified using ELISA and flow cytometry. FVIII antibodies, but not functional inhibitors were detectable 1 week after the first FVIII treatment in both strains. These antibodies mainly belonged to the IgM and IgA isotypes. After the fourth FVIII treatment, neutralizing anti‐FVIII antibodies were detected in both mouse strains: Balb/c (mean inhibitory titer 58 BU) and C57BL/6 (mean inhibitory titer 82 BU). IgG1 levels were similar in both strains but the IgG2A and IgG2B subclasses were higher in C57BL/6 mice. The results of intracellular cytokine staining of T cells indicated that the FVIII‐treated C57BL/6 mice produced more IL10 and Th1 cytokines than the FVIII‐treated Balb/c mice. These studies show that C57BL/6 mice develop a stronger immune response towards FVIII than Balb/c mice. We propose that the enhanced Th1 and IL10 cytokine micro‐environment induced in C57BL/6 mice is responsible for this difference. Therefore, genetic strain‐dependent differences must be considered when evaluating immunological outcomes in mouse models of haemophilia A.     

Murine model of Kawasaki disease induced by mannoprotein-beta-glucan complex, CAWS, obtained from Candida albicans

Intraperitoneal administration of CAWS (water-soluble extracellular polysaccharide fraction obtained from the culture supernatant of Candida albicans) to mice induces coronary arteritis similar to Kawasaki disease. We analyzed differences in the production of cytokines involved in the occurrence of coronary arteritis among mouse strains, C3H/HeN, C57BL/6, DBA/2 and CBA/J. The incidence of arteritis was 100% in C57BL/6, C3H/HeN and DBA/2 mice, but only 10% in CBA/J mice. The coronary arteritis observed in DBA/2 mice was the most serious, with several mice expiring during the observation period. The CAWS-sensitive strains revealed increased levels of IL-6 and IFN-gamma during the course of a specific response to CAWS by spleen cells. In contrast, IL-10 levels were observed to increase markedly in CAWS-resistant CBA/J mice, but not the CAWS-sensitive strains. However, TNF-alpha levels were more elevated only in DBA/2 mice. The difference in disease development and cytokine production strongly suggests that the genetic background of the immune response to CAWS contributes to the occurrence of coronary arteritis.     

Genetic background determines mouse strain differences in inflammatory angiogenesis

Inflammation and angiogenesis are key components of fibrovascular tissue growth, a biological event underlying both physiological (wound healing) and pathological conditions (tumor development, chronic inflammation). We investigated these components in three frequently used mouse strains (Swiss, Balb/c and C57BL/6J) to verify the influence of genetic background on the kinetics of inflammatory cell recruitment/activation, neovascularization, extracellular matrix deposition, and cytokine production in polyether-polyurethane sponge implanted subcutaneously in male mice of these strains. The kinetics of neutrophil recruitment/activation as assessed by myeloperoxidase (MPO) activity was 2- and 3-fold higher in Balb/c implants at day 1 compared with Swiss and C57BL/6J implants, respectively. Macrophage accumulation/activation as NAG (n-acetyl β-glucosaminidase) activity was higher in Swiss implants. The levels the monocyte chemoattractant protein 1 (CCL2(MCP-1)) peaked at day 10 in the three types of implants but was produced more by C57BL/6J mice. Angiogenesis (hemoglobin, vascular endothelial growth factor-VEGF, and number of vessels) differed among the strains. Swiss implants had the highest hemoglobin content but the lowest VEGF levels. In contrast, Balb/c implants had higher VEGF levels but lower hemoglobin. Collagen deposition and transforming growth factor β-1; TGFβ-1 levels also varied among the groups. Swiss and Balb/c implants had progressive increase in TGFβ-1 from 4 to 14 days, while C57BL/6J implants achieved the peak at day 10 and fell at day 14. These findings emphasize the major contribution of genetic background in the temporal pattern and intensity of inflammatory angiogenesis components that may have functional consequences in physiological and pathological conditions where these processes co-exist.     

Influence of dose and route of inoculation and of mouse strain on the production of interleukin 2 in mice infected with Mycobacterium lepraemurium

In order to evaluate the influence of route and dose of inoculation on interleukin 2 (IL2) production, C57BL/6 mice were infected either intravenously (I.V.) or subcutaneously (S.C.) with 10(5) or 10(8) Mycobacterium lepraemurium. The role of genetic factors on the production of IL2 during M. lepraemurium infection, was investigated in 7 inbred mouse strains (C57BL/6, DBA/2, F1 (C57BL/6 X DBA/2), DBA/1, BALB/c, CBA and A/J) after I.V. infection with 10(7) M. lepraemurium. At different times after M. lepraemurium inoculation, the number of AFB within the spleens of infected mice was counted and the ability of Con A-activated spleen cells to produce IL2 was studied. In S.C. inoculated C57BL/6 mice the increase in footpad thickness was measured during the progression of infection. After one month of infection heavily infected C57BL/6 mice (10(8) bacilli) showed an early and strong deficiency of IL2 production, regardless of the route of inoculation, whereas mice infected with a lower dose (10(5) bacilli) did not. In S.C. infected mice the decrease of IL2 production was observed when the footpad enlargement reached to the plateau phase. The data obtained from the numeration of AFB within the spleens of infected mice allowed to rank the infected mouse strains into 2 separated groups according to the pattern of the Bcg gene expression. An IL2 deficiency was only observed in C57BL/6, DBA/1, (C57BL/6 X DBA/2)F1 and DBA/2 infected mouse strains. No evident correlation could be shown between splenic IL2 activity upon Con A stimulation and the number of AFB recovered from the spleens of these 7 inbred mouse strains.     

Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants.

The development of cigarette smoke-induced pulmonary changes in C57 Bl/6J and DBA/2 mice was investigated. Both strains are sensitive to oxidants and C57Bl/6J mice are moderately deficient in serum alpha1-proteinase inhibitor. Following chronic exposure to cigarette smoke, patchy emphysema was present in mice of both strains, but developed faster in DBA/2 mice. A positive reaction for mouse neutrophil elastase was seen on the septa of both strains. Additionally, the DBA/2 mice developed a uniform parenchymal dilation that was preceded by the appearance of apoptotic cells in areas with a low signal for vascular endothelial growth factor-receptor 2. Fibrotic areas scattered throughout the parenchyma, coupled with a positive immunohistochemical reaction for transforming growth factor-beta was seen only in DBA/2 mice. Both DBA/2 and C57Bl/6J strains showed epithelial cell injury and areas of deciliation in their airways. However, the appearance of goblet cell metaplasia was common in C57Bl/6J mice but rare in DBA/2 mice. A positive immunohistochemical reaction for interleukin (IL)-4, IL-13 and MUC5AC was seen only in the airways of C57Bl/6J mice. Strain characteristics (alpha1-proteinase inhibitor levels, sensitivity to oxidants, and constitutive levels of vascular endothelial growth factor-receptor 2) and phenotypical responses (apoptosis and cytokine distribution) may condition parenchymal and airway changes to cigarette smoke.     

Experimental murine infection with the diffuse cutaneous leishmaniasis strain, Isabel

Infection with the Isabel strain of Leishmania has been followed in several inbred strains of mice over an extended period. The mouse strains segregate into three major types with respect to susceptibility to infection: BALB/c, BALB.B and SWR/J are susceptible; DBA/1J is intermediate; and C57BL/6, C57BL/10, DBA/2J and B10.D2 are resistant. Infections with other leishmanial strains have been well-characterized in the BALB/c mice. Therefore, BALB/c mice were selected for extended studies. Progression of the disease was assessed by the following parameters: (1) numbers of parasites isolated from various tissues including footpad lesions, spleens, and lymph nodes and (2) the presence of metastatic lesions. This model should prove valuable in the study of the early immunological events in leishmaniasis.     

Increased expression of hypothalamic leptin receptor and adiponectin accompany resistance to dietary-induced obesity and infertility in female C57BL/6J mice

BACKGROUND: Obesity is strongly associated with female infertility, but the mechanisms underlying this relationship are largely unknown. METHODS: We investigated the effect of increasing dietary fat percentage upon body mass, hypothalamic neuropeptide gene expression, adipose hormone secretion and fertility in females of the inbred mouse strains C57BL/6J and DBA/2J. To assess the effect of obesity independent of dietary influence, we also compared these parameters in wild-type female C57BL/6J mice to those congenic for the obesogenic mutations ob/ob and A(y)/a. RESULTS: After 24 weeks, rather than exhibiting an obese, leptin-resistant phenotype like their female DBA/2J counterparts, wild-type female C57BL/6J mice remained lean, fertile and manifested increased hypothalamic LEPR-B expression. Although both mutant genotypes were associated with obesity and subfertility, ob/ob mice demonstrated significantly increased hypothalamic LEPR-B expression, whereas A(y)/a mice had a significant reduction. Interestingly, wild-type female C57BL/6J mice were noted to manifest significantly higher and lower levels of adiponectin and tissue plasminogen activator inhibitor-1 (tPAI-1), respectively, than weight-matched wild-type female DBA/2J mice. CONCLUSIONS: We conclude that (1) resistance to the obese-infertile phenotype in female C57BL/6J mice is associated with increased hypothalamic leptin receptor expression and alterations in adipokine levels consistent with decreased adipose tissue inflammation and (2) that long-standing hyperleptinemic obesity in mice is associated with a downregulation of the hypothalamic leptin receptor.     

UV致弱尾蚴免疫对小鼠血吸虫再感染的保护力观察

目的观察致弱日本血吸虫尾蚴免疫小鼠再次感染血吸虫后的减虫率、减卵率及肝脏病理损伤,为血吸虫疫苗的研制奠定基础。方法分别以400μw／cm^2×60s和422μw／cm^2×40s两种不同UV强度及时间照射的日本血吸虫尾蚴免疫C57BL／6和DBA小鼠,观察免疫小鼠对再次血吸虫感染的减虫率、肝脏减卵率及肝脏病理改变。结果400μw／cm^2×60s（A）和422μw／cm^2UV×40s（B）照射的日本血吸虫尾蚴免疫组C57BL／6小鼠再次感染血吸虫后的减虫率分别为一0．60％和0．02％,肝脏肝脏减卵率分别为2．70％和11．37％;DBA小鼠再次感染血吸虫后的减虫率分别为29．10％和25．70％,肝脏肝脏减卵率分别为59．50％和69．50％。422μw／cm^2UV×40S辐照尾蚴免疫C57BL／6小鼠,再次感染血吸虫形成的肝脏单个虫卵肉芽肿面积与对照组比较显著减小（P〈0．01）;400μw／cm^2UV×60s和422μw／cm^2UV×40S辐照尾蚴免疫DBA小鼠再次感染血吸虫造成的肝脏单个虫卵肉芽肿面积与对照组比较显著减小（P〈0．01）。结论UV致弱尾蚴免疫对C57BL／6、DBA小鼠再次感染血吸虫的保护作用较小,但能降低肝脏卵荷并减轻肝脏的病理损伤。     

Genetic background determines mouse strain differences in inflammatory angiogenesis

Inflammation and angiogenesis are key components of fibrovascular tissue growth, a biological event underlying both physiological (wound healing) and pathological conditions (tumor development, chronic inflammation). We investigated these components in three frequently used mouse strains (Swiss, Balb/c and C57BL/6J) to verify the influence of genetic background on the kinetics of inflammatory cell recruitment/activation, neovascularization, extracellular matrix deposition, and cytokine production in polyether-polyurethane sponge implanted subcutaneously in male mice of these strains. The kinetics of neutrophil recruitment/activation as assessed by myeloperoxidase (MPO) activity was 2- and 3-fold higher in Balb/c implants at day 1 compared with Swiss and C57BL/6J implants, respectively. Macrophage accumulation/activation as NAG (n-acetyl β-glucosaminidase) activity was higher in Swiss implants. The levels the monocyte chemoattractant protein 1 (CCL2(MCP-1)) peaked at day 10 in the three types of implants but was produced more by C57BL/6J mice. Angiogenesis (hemoglobin, vascular endothelial growth factor-VEGF, and number of vessels) differed among the strains. Swiss implants had the highest hemoglobin content but the lowest VEGF levels. In contrast, Balb/c implants had higher VEGF levels but lower hemoglobin. Collagen deposition and transforming growth factor β-1; TGFβ-1 levels also varied among the groups. Swiss and Balb/c implants had progressive increase in TGFβ-1 from 4 to 14 days, while C57BL/6J implants achieved the peak at day 10 and fell at day 14. These findings emphasize the major contribution of genetic background in the temporal pattern and intensity of inflammatory angiogenesis components that may have functional consequences in physiological and pathological conditions where these processes co-exist.