Inapparent Respiratory Infection of Inbred Swiss Mice with Sulfadiazine-Resistant, Iodine-Negative Chlamydiae

Three chlamydial strains were isolated from the lungs of three different strains of mice that were inbred for over 30 years. These chlamydial strains were resistant to sulfadiazine and did not induce iodine-positive, glycogen-like material in the inclusions of infected L cells which characterizes them as Chlamydia psittaci.     

Rearing Environmental Enrichment in Two Inbred Strains of Mice: 1. Effects on Emotional Reactivity

The effects of an enriched rearing environment on two types of anxiety-like behavior (designated trait and state anxiety) and on spontaneous activity were investigated in two inbred strains of mice, BALB/c (C) and C57BL/6(B6). Subjects were socially reared from birth to 56 days of age under enriched or standard rearing conditions. The enriched environment consisted of an assembly of plastic boxes in which a various number of objects (running wheels, pieces of plastic, etc.) offered the possibility of multiple activities. The subjects were subsequently tested in three situations: a spontaneous activity recorder, an elevated plus-maze test (a model of state anxiety), and a free exploration test (a model of trait anxiety). No group differences could be found in spontaneous activity. Environmental enrichment, however, decreased the level of both types of anxiety-like behavior in the C strain. In contrast, the level of trait anxiety of the B6 mice was not modified. The results were discussed in relation to possible CNS modifications, especially in the limbic system.     

Differential Susceptibility to Hepatic Inflammation and Proliferation in AXB Recombinant Inbred Mice Chronically Infected with Helicobacter hepaticus

Helicobacter hepaticus is a naturally occurring pathogen of mice and has been used to develop models of chronic hepatitis, liver cancer, and, more recently, inflammatory bowel disease, in selected mouse strains. A/JCr mice are particularly susceptible to H. hepaticus-induced hepatitis and subsequent development of liver neoplasms, whereas C57BL/6 mice are resistant. In this study, we inoculated nine AXB recombinant inbred (RI) mouse strains, derived from A/J and C57BL/6 mice, with H. hepaticus to determine the genetic basis of resistance to Helicobacter-induced liver disease. Mice were surveyed 14 months after inoculation by culture and PCR for H. hepaticus colonization of the liver and cecum, and microscopic morphometric evaluations of the liver were performed to quantify and correlate the severity of inflammation, apoptosis, and proliferation. Analysis of variance of hepatic inflammation demonstrated significant variation among the RI strains (P < 0.0001), and the strain distribution pattern suggested a multigenic basis of disease resistance. Quantitative trait analysis using linear regression suggested possible linkage to loci on mouse chromosome 19. Hepatocellular and biliary epithelial apoptosis and proliferation indices, including proliferation of oval cells, were markedly increased and correlated with severity of inflammation. Prevalence of hepatic neoplasia was also increased in susceptible RI strains. These findings demonstrate a genetic basis for susceptibility to Helicobacter-induced disease and provide insight into its pathogenesis.     

Psychotropic Effects of Sidnocarb and Ladasten in Inbred Mice with Different Reaction to Emotional Stress

Dose-dependent relationship of the effects of sidnocarb and Ladasten on open field behavior and free motor activity was studied in inbred C57Bl/6 and BALB/c mice differing by emotional stress reaction phenotype. Ladasten in a dose of 10 mg/kg produced activating and anxiolytic effects on BALB/c mice in the open field test. Combined injection of Ladasten (10 mg/kg) and sidnocarb (6 or 12 mg/kg) activated animal behavior in both tests.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 3, pp. 316–318, March, 2005     

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone.     

头孢地秦在免疫抑制小鼠白念珠菌败血症中的作用

为观察头孢地秦 (cefodizime ,CDZ )在实验性免疫抑制小鼠白念珠菌败血症中的免疫调节作用及其在抗感染免疫中的综合作用 ,本文用环磷酰胺 (CTX )免疫抑制昆明种小鼠 ,分别腹腔注射CDZ 6 0 0mg/kg、 2 0 0mg/kg、 5 0mg/kg及头孢曲松 (cef triaxone ,CRO ) 2 0 0mg/kg× 7d。并在第 3天尾静脉注射白念珠菌 ,第 8天分别测定各组的炭廓清功能、血清溶血素的生成及T细胞亚群的变化。观察小鼠注射白念珠菌后的生存期并作生存分析。研究表明CDZ 6 0 0mg/kg、CDZ 2 0 0mg/kg组能明显提高CTX抑制的炭廓清功能 (P <0 0 5 ) ;CDZ各组亦能增加被CTX抑制的血清溶血素水平 (P <0 0 1) ;与CTX组相比 ,CDZ6 0 0mg/kg组明显提高CD4/CD8比值 (P <0 0 5 )。整体比较各组生存率 ,与其免疫调节功能基本一致。尾静脉注射白念珠菌后 ,CTX组 3d就有小鼠死亡 ,其平均生存期为 5d ,而CDZ 6 0 0mg/kg组、 2 0 0mg/kg组、 5 0mg/kg组最长生存期分别为 16d、17d和 12d ,其平均生存期分别为 12 8d、 11 7d和 9 6d ,明显高于免疫抑制组小鼠 (P <0 0 1)。而CRO组和免疫抑制组相比 ,差别无显著差异。说明CDZ能提高免疫抑制机体的免疫功能 ,并在抗感染免疫中发挥作用 ,提示其在临床感染治疗上可能具有重要的实际意义。     

Naloxone Effects on Behavior of Inbred Mice with Different Response to Emotional Stress in Open Field Test

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and С57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and С57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in С57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in С57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.     

近交系小鼠数量性状基因的定位克隆策略

许多影响人类健康的重大疾病如高血压、哮喘和肥胖等都是复杂性状相关疾病.模式动物小鼠作为复杂性状研究的重要遗传资源,至今已有2900个数量性状基因座(QTL)在小鼠中被初步定位,然而国内对于小鼠复杂性状相天基因研究的报道并不多.本文埘近交系小鼠在复杂性状研究中的优势以及利用近交系小鼠进行QTL初步定位和精细定位的策略进行了综述,并重点介绍小鼠QTL克隆所面临的挑战,提出利用合作杂交计划和野生小鼠资源解决QTL基因研究费时费力且定位分辨率低等一系列瓶颈问题的新思路.     

Effects of Acquired Resistance on Infection with Eimeria falciformis var. pragensis in Mice

Mice immunized with infections of 500, 5,000, or 20,000 oocysts of E. falciformis var. pragensis were reinfected with 20,000 and 100,000 oocysts at 20 and 38 days, respectively, after the initial infection. After the first challenge infection, none of the immunized mice showed clinical signs of coccidiosis; a few mice passed very low numbers of oocysts, and oocyst discharge seemed to correlate negatively with immunizing dose. None of the mice immunized twice passed oocysts after challenge. Mice immunized with three infections were completely immune to challenge for 4 months. The effect of the immune response on the life cycle of the coccidium was determined by histological examination of the intestines of immune and nonimmune mice infected with the parasite. In both the immune and nonimmune groups, sporozoites penetrated absorptive epithelial cells and migrated to crypt epithelial cells during the first 6 to 24 h postinfection. At 48 to 72 h postinfection, the sporozoites developed into mature first-generation schizonts in the nonimmune mice, whereas the developing first-generation schizonts degenerated within the crypt epithelial cells of the immune mice. In nonimmune mice, third-generation merozoites, inoculated intracecally, developed into mature fourth-generation schizonts, whereas in immune mice the developing fourth-generation schizonts degenerated before maturing. The possibility that a cellmediated immune mechanism is responsible for the arrest in schizogony is discussed.     

Pulmonary Infection of Mice with Staphylococcus aureus

The survival of Staphylococcus aureus in the lungs of mice was studied under various conditions. Doses of 10⁷ to 10⁹ washed staphylococci were quantitatively introduced into the lungs after intratracheal inoculation in mice under either ether or sodium pentobarbital anesthesia. Mice were sacrificed at intervals, the lungs were excised and homogenized, and the cocci were enumerated by plate count. The 50% lethal dose was 6 × 10⁸ cocci per mouse, and mice died within 24 h but without proliferation of the inoculum. Mice given 10⁸ cocci intratracheally under pentobarbital anesthesia regularly survived and eliminated the organisms over a 48-h period. The use of ether anesthesia resulted in persistence of the inoculum for up to 48 h, but the organisms were then eliminated. Inability to proliferate did not appear to result from a lack of iron because pretreatment of the mice with ferric ammonium citrate or Imferon did not alter inoculum survival. Staphylococci inoculated intratracheally in mice infected with influenza virus 3 to 21 days previously showed no enhanced persistence or multiplication. Cocci preclumped with fibrinogen, inocula mixed with 10 times the number of Formalin-killed staphylococci, or inocula of the encapsulated Smith strain did not survive any better than conventional inocula, suggesting that phagocytosis might not be the sole mechanism for elimination. However, a sedimentable fraction from normal or infected lung homogenates proved either inhibitory or cidal for staphylococci in vitro.     

Effects of Dextran Sulfate 500 on Cell-Mediated Resistance to Infection with Listeria monocytogenes in Mice

Injection of dextran sulfate 500 caused loss of antibacterial resistance. Mice became more susceptible to an infection with Listeria monocytogenes and were unable to develop antilisterial immunity after both active and passive immunization with passively administered spleen cells from Listeria-immune donors. Indirect evidence suggests that the phagocytic component of cell-mediated resistance to bacterial infection is the site of attack of dextran sulfate.     

Differential Effects of Thalidomide on Angiogenesis and Tumor Growth in Mice

Thalidomide, clinically used as an antiinflammatory and antitumoral drug, inhibited sponge-induced angiogenesis when administered systemically (100 mg/kg^–1) in mice. However, it failed to inhibit solid Ehrlich tumor in the same mouse strain. We have used functional, biochemical and histological parameters to assess neovascularization and fibrovascular tissue infiltration of the mice sponge granuloma. The neovascularization growth as detected by development of blood flow and hemoglobin content extracted from the implants showed that thalidomide inhibited fibrovascular tissue formation by 40%. The functional and biochemical parameters correlated well with the histological study. Thalidomide had no inhibitory effect in the development of Ehrlich tumor. The detection of this selective action using the same animal strain bearing two different processes, supports the hypothesis that rather than species specificity, thalidomide is tissue specific. This approach may be used to identify the specificity of other therapeutic agents against distinct angiogenesis-dependent diseases.     

Consequence of Nramp1 Deletion to Mycobacterium tuberculosis Infection in Mice

129sv mice functionally deleted of the antimicrobial resistance gene, Nramp1, were found to be as resistant as wild-type mice to infection with the virulent H37Rv strain of Mycobacterium tuberculosis, as determined by monitoring bacterial growth in major organs and recording host survival times. Death of infected mice of both types was associated with extensive infection-induced pathology in the lungs but not in other major organs. These findings are in keeping with the view that Nramp1 is of limited importance in resistance to tuberculosis in mice.     

Antigenic Modification, Rosette-Forming Cells, and Salmonella typhimurium Resistance in Outbred and Inbred Mice

To assess the separate contributions of host T cells and the physical state of the antigen in the development of effective. Salmonella resistance, glutaraldehyde-treated and untreated protein- and ribonucleic acid-rich extracts (E-RNA extracts) of virulent Salmonella typhimurium SR-11 or attenuated S. typhimurium RIA were used to immunize Salmonella-resistant Salmonella-susceptible strains of mice for the purpose of determining whether antigen-specific T-cell or B-cell responses were formed and, if so, which responses predominated. The resistance imparted to each mouse strain after vaccination with S. typhimurium RIA was used as the standard for comparison. The inbred mouse strains C57BL/6 and DBA/2 and their F₁ hybrid (strain BDF₁), outbred ICR Swiss mice, and endotoxin-resistant C3H/HeJ mice were examined for the capacity to develop resistance to lethal Salmonella infections, as well as the ability to generate antigen-reactive T cells. Only the BDF₁, C3H/HeJ, and ICR Swiss mice were able to develop resistance to challenge infections mediated by the virulent SR-11 strain of S. typhimurium after vaccination with the living, attenuated RIA strain of S. typhimurium or immunization with E-RNA extracts. We developed an assay to identify the antigen-reactive rosette-forming lymphocytes present in lymph nodes and spleens of immunized mice. Levels of 0.2% or higher of theta antigen-bearing, antigen-reactive rosette-forming cells were found in the lymph nodes or spleens or both of only the BDF₁, C3H/HeJ, and ICR Swiss mice (i.e., in the “Salmonella responder” strains). Mouse strains C57BL/6 and DBA/2, which failed to develop resistance to lethal infections after immunization with the S. typhimurium RIA vaccine or with the E-RNA extracts, lacked effective numbers of antitheta antigen-sensitive rosette-forming cells. Modification of the effective E-RNA extracts by polymerization with glutaraldehyde resulted in a marked diminution in their abilities to induce resistance to salmonellosis in the two responder mouse strains tested (BDF₁ and ICR Swiss), even though detectable levels of antibody were induced.     

Disseminated Gonococcal Infection in Mice

Gonococci do not readily cause disseminated infection in mice. To simulate some of the conditions leading to disseminated gonococcal infection in women, we suspended gonococci in mucin plus hemoglobin and studied the development of gonococcal bacteremia. The mucin-hemoglobin mixture was used because the menstruum appears to be involved in dissemination of gonococci from the genital tract during menstruation. Mice did not die after massive inocula of 10(9) gonococci given intraperitoneally in broth, but when gonococci were suspended in mucin (15%) alone, the 50% lethal dose was 10(8.4) and in 15% mucin plus 4% hemoglobin (M/H), the 50% lethal dose fell to 10(6.6). Sublethal doses produced local peritonitis and transient bacteremia. With larger inocula the local peritoneal infection progressed to fatal septicemia. Studies of the mechanism by which M/H lowered the 50% lethal dose showed that systemic clearance mechanisms were compromised, but not enough to account for the total decrease in the 50% lethal dose. If gonococci were given intravenously after intraperitoneal inoculation of M/H, sequestration of gonococci in the peritoneal cavity occurred, suggesting an effect on local peritoneal defenses. The effect on neutrophils appeared most significant, since numbers of neutrophils in the peritoneal fluid were decreased in the presence of M/H and neutrophils were destroyed by M/H in vitro. The serum bactericidal system was not affected. We conclude that M/H promotes gonococcal bacteremia by interference with phagocytosis and intracellular killing of gonococci. The model simulates the disseminated gonococcal infection cases in women which follow pelvic inflammatory disease in its progression from local peritonitis to transient or lethal bacteremia and in factors (mucin and hemoglobin) which enhance infection.