变性梯度凝胶电泳在实验小鼠细菌检测中的应用

目的 研究变性梯度凝胶电泳(denatured gradient gel electrophoresis, DGGE)在实验小鼠细菌检测中的应用。方法 根据16S rDNA V3区引物,PCR扩增3种实验小鼠(KM小鼠、NIH小鼠和BALB/c小鼠)呼吸道和盲肠段的细菌基因组DNA;扩增产物运用DGGE进行电泳检测,并分析条带数量间差异的统计学意义。结果 KM小鼠盲肠段条带12~18条,呼吸道条带5~10条;NIH小鼠盲肠段条带15~20条,呼吸道条带4~10条;BALB/c小鼠盲肠段条带10~15条,呼吸道条带0~7条。统计分析结果显示,KM小鼠和NIH小鼠在盲肠和呼吸道电泳条带数量上的差异无统计学意义( P >0.05);BALB/c小鼠与KM小鼠、NIH小鼠间的差异均有统计学意义( P <0.05)。结论 DGGE 在实验小鼠盲肠和呼吸道细菌检测中能较好地反映菌群的物种多样性。     

多次注射乌拉坦诱导的BALB/C及C57BL/6J小鼠肺癌模型的比较

目的探讨一种稳定的多次乌拉坦注射诱导小鼠肺癌模型的构建方法,比较BALB/C及C57BL/6J小鼠对该肺癌模型的敏感性。方法 10只BALB/C小鼠及10只C57BL/6J小鼠适应性饲养3周,随后每只小鼠分别被给予每周1次腹腔注射1 g/kg体重乌拉坦,连续注射10周,继续喂养15周后处死小鼠取肺组织。由3名不同的检测者在解剖显微镜下观察计数肺组织表面肿瘤数目并以直径记录肿瘤大小;HE染色检测肺组织病理变化。结果多次乌拉坦注射诱导的BALB/C及C57BL/6J小鼠肺癌发生率均为10/10(100%);BALB/C小鼠荷瘤数明显多于C57BL/6J小鼠(P0.01),同时,直径也大于C57BL/6J小鼠(P0.05);HE染色显示多次乌拉坦注射诱导的肺癌有非典型性腺瘤增生及腺瘤两种病变类型。结论 BALB/C和C57BL/6J小鼠均可以作为多次注射乌拉坦诱导性肺癌模型的动物,BALB/C小鼠对该肺癌模型的敏感性高于C57BL/6J小鼠。     

转基因人源化ACE2裸小鼠模型的建立

目的 建立BALB/c-Nude裸小鼠为背景的人源化ACE2(hACE2)转基因裸小鼠动物模型。方法 利用hACE2转基因小鼠与雄性BALB/c-Nude裸小鼠杂交获得F1代,将F1代hACE2小鼠与BALB/c-Nude裸小鼠回交获得F2代,再将F2代hACE2小鼠互交获得F3代hACE2转基因裸小鼠。对F3代中hACE2转基因裸小鼠的生长发育、生理指标及免疫指标与C57BL/6J野生型小鼠、hACE2小鼠和BALB/c-Nude裸小鼠对比分析。结果 (1)hACE2转基因裸小鼠生长发育指标与C57BL/6J野生型小鼠、hACE2小鼠和BALB/c-Nude裸小鼠无明显差异。(2)hACE2转基因裸小鼠生理指标中,建立的hACE2转基因裸小鼠与BALB/c-Nude裸小鼠相似,病理解剖观察发现,小鼠体内均无胸腺。脏器系数结果与BALB/c-Nude裸小鼠比较,脾系数和肝系数出现显著性差异(P<0.05)。血常规检测指标与C57BL/6J野生型小鼠、hACE2小鼠比较,中性粒细胞百分比(NEU)、淋巴细胞百分比(LYM)和单核细胞百分比(MONO)均出现显著性差异(P<0....     

人巨细胞病毒小鼠模型的建立

采用HCMV-AD_(169)株实验感染昆明系和BALB/C系小鼠,攻毒后感染急性期BALB/C系小鼠的死亡率(28.57％)高于昆明系小鼠(5.26％)。两种不同品系小鼠的临床症状和HCMV导致的病理损害脑钙化无明显差异。昆明小鼠的发病率(94.74％)高于BALB/C小鼠。     

BALB/c和ICR小鼠的学习记忆能力等行为学研究

目的研究不同品系小鼠学习记忆能力的差异,为学习记忆的基础研究提供应用信息。方法80只BALB/c和80只ICR小鼠分别分为Morris水迷宫组、跳台组、穿梭组、ROTA-ROD组,每组20例,进行学习记忆能力及行动能力测试。结果水迷宫组在9轮水迷宫训练学习期BALB/c小鼠空间学习记忆能力没有明显提高。ICR小鼠从9轮水迷宫训练学习期的第4次开始,逃避潜伏期显著缩短,与前3次相比差异有显著性(P<0.001)。跳台组ICR和BALB/c小鼠训练前后5 min内错误次数及跳下潜伏期差异均具有显著性。穿梭组ICR小鼠学习期与记忆期主动逃避次数、被动逃避次数及电击时间的差异均有显著性,而BALB/c小鼠训练前后主动逃避次数、被动逃避次数及电击时间的差异均无显著性。ROTA-ROD组ICR小鼠的跑步动作维持时间显著高于BALB/c小鼠,其差异有显著性。结论以上结果提示在进行某些学习记忆实验时,使用ICR小鼠优于BALB/c小鼠。     

4种小鼠的寒、热体质研究

[目的]研究4种品系小鼠的寒、热体质。[方法]8~9周龄昆明、BALB/c、C57BL/6J、ICR小鼠,以及4~5周龄昆明小鼠,同步系统检测其生物学特性,然后以统一的评价标准评价4种品系小鼠的寒、热体质。并对BALB/c小鼠给予参桂理中丸和利血平做药物反证。[结果]①4~5周龄昆明小鼠与8~9周龄昆明小鼠比较体质明显偏热;②BALB/c小鼠与C57BL/6J小鼠比较体质偏寒;③8~9周龄雄性BALB/c小鼠、雄性和雌性C57BL/6J小鼠与8~9周龄相应性别昆明小鼠比较体质无明显差异;8~9周龄雌性BALB/c小鼠与8~9周龄雌性昆明小鼠比较体质偏寒;④8~9周龄ICR小鼠与8~9周龄BALB/c小鼠、C57BL/6J小鼠比较体质偏热;8~9周龄雄性ICR小鼠与8~9周龄雄性昆明小鼠比较体质偏热。[结论]4种品系小鼠存在寒、热体质差异。     

柯萨奇病毒B3型诱导的免疫偏离与心肌炎发病关系的研究

目的 研究2种近交系小鼠在柯萨奇病毒B3型(CVB3)感染后辅助性T细胞(Th)免疫偏离对心肌炎发病的影响。方法 用CVB3腹腔感染BALB/c和C57BL/62种近交系小鼠,感染后7d通过检测小鼠血清肌酸激酶(CK)活性,观察心脏外观变化以及心脏石蜡切片H.E染色观察心脏病理改变,比较2种小鼠心肌炎的发病情况;通过体外感染心肌细胞观察病毒复制情况以及体内心脏组织病毒载量的分析,比较2种小鼠对病毒感染和复制的差异;通过检测感染小鼠细胞因子白细胞介素-4(IL-4)、IL-12和γ干扰素(IFN-γ)的表达,抗CVB3VP1抗体的亚型以及T-bet和Gata-3的表达,比较2种小鼠Th免疫偏离的情况。结果 CVB3在体外和体内都可以感染BALB/c和C57BL/6小鼠心肌细胞,但仅BALB/c小鼠感染后可发生明显的病毒性心肌炎,C57BL/6小鼠则不能;BALB/c小鼠感染后表现为Th1型免疫反应而C57BL/6小鼠则偏向于Th2型免疫反应。结论 CVB3感染2种品系小鼠表现为不同的心肌炎发生率,与其诱导了不同类型的免疫偏离密切相关。     

饮用经臭氧处理的灭菌水与小鼠自发性乳腺肿瘤的发生

目的研究饮用经臭氧处理的灭菌水对小鼠自发性乳腺肿瘤发生的影响。方法给昆明(KM)小鼠、NIH小鼠和BALB/c小鼠饮用经臭氧处理的灭菌水,然后观察其乳腺肿瘤的发生情况,剖检小鼠并从其乳腺、左右肺叶、气管、肺门淋巴结、鼠蹊部淋巴结、心、肝、脾、肾、脑和大小肠等部位取材固定,常规病理制片进行病理组织学检查。结果饮用经臭氧处理的水数月后,KM小鼠、NIH小鼠和BALB/c小鼠,自发性乳腺肿瘤的数量明显增加。发生的乳腺肿瘤均为乳腺腺癌,其中一例为乳头状囊腺癌。乳腺肿瘤均发生在生育3～4胎以上的雌性小鼠。9例中有3例发生肺转移癌。根据乳腺肿瘤发生部位、大体形态特征及病理组织学,结合临床发病情况,即可明确诊断。结论长期饮用经臭氧处理的灭菌水可使小鼠自发性乳腺肿瘤的发生率明显上升。     

一种新的近交系实验动物遗传监测方法及小鼠性别相关RAPD标记的发现

我们用21个10 bp的随机短引物对来自昆明、成都、上海、北京四个地方的BALB/c小鼠以及C57BL小鼠、昆明种小白鼠进行了随机扩增多态DNA(RAPD)分析,发现13个引物的扩增产物在BALB/c小鼠和C 57 BL小鼠中有差异,8个引物的扩增产物在BALB/c小鼠和昆明种小白鼠之间不同.在四个地方的BALB/c小鼠中,成都、上海、北京的BALB/c小鼠其遗传背景均一,而来自昆明的BALB/c小鼠中,有2只的4个引物的扩增产物不同于其它的BALB/c小鼠,表明这两只BALB/c小鼠可能曾发生过某种程度的遗传改变或污染。实验结果显示RAPD方法是一种有效的近交系实验动物遗传监测手段。实验中一个有趣的结果是,在OPG 2、OPE 4、OPE 9的扩增产物中,发现了严格的性别依赖的PAPD标记。OPE 9扩增产物中,凡雄性个体都有一条0.88 kb的标记.OPG 2、OPE 4则在所有的雄性个体中多扩增出一条约1.2 kb的带。通过交叉PCR扩增和斑点杂交证明OPG 2、OPE 4 得到的雄性特异性RAPD标记虽分子大小一致,但不具同源性。这些性别相关RAPD标记的染色体定位和性质分析正在进一步进行中.     

Listr1遗传位点影响小鼠对约氏疟原虫易感性的研究

探讨Listr1遗传位点影响小鼠对疟原虫易感性的可能性及其初步作用机制。致死型约氏疟原虫(Plasmodiumyoelii17XL,P.y17XL)感染C.B6By-Listr1小鼠(BALB/c小鼠基因背景下引入C57BL/6小鼠Lis-tr1遗传位点的同类系小鼠)和BALB/c小鼠,分析二者生存率和感染率的差异;HE染色分析P.y17XL感染后第5天C.B6By-Listr1小鼠和BALB/c小鼠肝脏组织损伤情况;定量PCR法检测P.y17XL感染后小鼠肝脏组织第1、2、5天IL-1β、IL-6、TNF-α、IFN-γ的表达含量。结果显示,P.y17XL感染后4~8dC.B6By-Listr1小鼠虫血症水平显著高于BALB/c小鼠(P<0.05)。C.B6By-Listr1小鼠于感染后7~9d全部死亡;而半数BALB/c小鼠于感染后8~9d死亡,其余BALB/c小鼠至感染后第13天仍存活,两种小鼠生存率差异具有统计学意义(P<0.01)。C.B6By-Listr1小鼠P.y17XL感染后第5天肝组织HE染色可见到明显的疟色素沉积;而BALB/c小鼠全片基本未见到疟色素的沉积。P.y17XL感染后第2天BALB/c小鼠肝组织IL-6(P<0.05)、TNF-α(P<0.05)mRNA水平显著高于C.B6By-Listr1小鼠。结果表明Listr1遗传位点可以影响小鼠对疟原虫的易感性,与肝脏固有免疫相关。     

Development of an adult mouse model for studies on protection against rotavirus.

Although mice have been used as an animal model for studies on rotavirus disease, these studies have been limited by the short time period after birth during which mice are susceptible to rotavirus illness (i.e., approximately 15 days). To overcome this limitation, an adult mouse model was developed in which the endpoint was infection rather than illness. The model developed utilized a strain of mouse rotavirus (EDIM) adapted to grow in culture by multiple passages in MA104 cells. The second cell culture passage of EDIM caused severe diarrhea in neonatal BALB/c mice, and little or no amelioration of disease was observed after nine cell culture passages, even when this preparation was plaque purified. Oral administration of 2 x 10(3) PFU of passage 9 also consistently caused infection of mice 4, 10, 15, 30, 60, 120, and 180 days of age as determined by viral shedding and seroconversion. Reinoculation of these mice with the same virus preparation at 2, 3, or 4 months after the first inoculation produced no evidence of reinfection. In contrast, infection of neonatal mice with the heterotypic WC3 bovine rotavirus did not prevent reinfection with culture-adapted EDIM. Thus, this strain of EDIM caused consistent infection of previously uninoculated neonatal and adult BALB/c mice and produced homotypic but not heterotypic protection against reinfection.     

Antibody-Dependent and -Independent Protection following Intranasal Immunization of Mice with Rotavirus Particles

The ability to elicit protective immune responses after intranasal immunization with rotavirus particles, either with or without the attenuated Escherichia coli heat-labile enterotoxin LT(R192G) as an adjuvant, was examined in the adult mouse model. BALB/c mice were administered one or two inoculations of psoralen/UV-inactivated, triple-layered (tl) or double-layered (dl) purified rotavirus particles. Four weeks after immunization, mice were challenged with the murine rotavirus strain EDIM, and the shedding of rotavirus antigen was quantified. Rotaviruses used for immunization included EDIM and heterotypic simian (RRV), bovine (WC3), and human (89-12) strains. tl EDIM stimulated both systemic and intestinal rotavirus antibody responses and complete protection with as little as one 1-microgram dose. Inclusion of LT(R192G) (10 micrograms) significantly increased rotavirus antibody responses and reduced antigen concentrations needed for full protection. Both dl EDIM and heterotypic dl and tl particles stimulated protection, but they did so less than tl EDIM at comparable concentrations, either with or without LT(R192G). When B-cell-deficient microMt mice were immunized with tl EDIM particles, protection was reduced to levels similar to those induced with dl EDIM and heterotypic particles in BALB/c mice. However, dl EDIM particles induced similar levels of protection in both mouse strains. The protection stimulated by tl or dl EDIM particles was not diminished by CD8 cell depletion prior to immunization in either strain of mice. These results indicate that tl EDIM induced immunity at least partially through responses to its outer capsid proteins, presumably by stimulation of serotype-specific neutralizing antibody. In contrast, the other particles stimulated protection primarily by an antibody-independent mechanism. Finally, depletion of CD8 cells had no effect on protection by either mechanism.     

Evidence that resolution of rotavirus infection in mice is due to both CD4 and CD8 cell-dependent activities.

The effector functions responsible for resolution of shedding in mice orally inoculated with the murine rotavirus strain EDIM were identified in B-cell-deficient and normal BALB/c mice after monoclonal antibody (MAb) depletion of CD4 and CD8 cells. When depleted of CD8 cells, B-cell-deficient muMt mice resolved their infections more slowly than nondepleted animals, but CD4 cell depletion caused chronic, high-level shedding. This finding indicated that CD4 cell-dependent immunological effectors other than, or in addition to, CD8 cells played roles in rotavirus resolution in muMt mice in the absence of antibody. The roles of CD4 and CD8 cells in resolution of rotavirus shedding were further characterized in immunologically normal BALB/c mice. Depletion of CD4 cells before EDIM inoculation resulted in rapid resolution of most shedding, but chronic, low-level shedding continued for weeks. When the CD4 cell-depleted BALB/c mice were subsequently depleted of CD8 cells, shedding levels increased significantly (P < 0.001), indicating that CD8 cells were responsible for the rapid but incomplete suppression of rotavirus shedding. Further experimentation revealed that little rotavirus antibody was made in CD4 cell-depleted BALB/c mice, and only after CD4 cells were repopulated did antibody production increase and virus shedding fully resolve. Thus, resolution of rotavirus shedding in both muMt and BALB/c mice was associated with CD4 and CD8 cell effector activities.     

Japanese encephalitis virus infection induces changes of mRNA profile of mouse spleen and brain

Background

Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R^®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.

Methods

BALB/c mice were treated by gavage once daily with Gastrogard-R^® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.

Results

Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R^® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R^®. Mice receiving Gastrogard-R^® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.

Conclusions

Preventing RRV-induced diarrhea by Gastrogard-R^® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.     

Recovery from chronic rotavirus infection in mice with severe combined immunodeficiency: virus clearance mediated by adoptive transfer of immune CD8+ T lymphocytes.

Severe combined immunodeficient (SCID) mice lack both functional T and B cells. These mice develop chronic rotavirus infection following an oral inoculation with the epizootic diarrhea of infant mice (EDIM) rotavirus. Reconstitution of rotavirus-infected SCID mice with T lymphocytes from immunocompetent mice allows an evaluation of a role of T-cell-mediated immunity in clearing chronic rotavirus infection. Complete rotavirus clearance was demonstrated in C.B-17/scid mice 7 to 9 days after the transfer of immune CD8+ splenic T lymphocytes from histocompatible BALB/c mice previously immunized intraperitoneally with the EDIM-w strain of murine rotavirus. The virus clearance mediated by T-cell transfer was restricted to H-2d-bearing T cells and occurred in the absence of rotavirus-specific antibody as determined by enzyme-linked immunosorbent assay, neutralization, immunohistochemistry, and radioimmunoprecipitation. Temporary clearance of rotavirus was observed after the transfer of immune CD8+ T cells isolated from the intestinal mucosa (intraepithelial lymphocytes [IELs]) or the spleens of BALB/c mice previously infected with EDIM by the oral route. Chronic virus shedding was transiently eliminated 7 to 11 days after spleen cell transfer and 11 to 12 days after IEL transfer. However, recurrence of rotavirus infection was detected 1 to 8 days later in all but one SCID recipient receiving cells from orally immunized donors. The viral clearance was mediated by IELs that were both Thy1+ and CD8+. These data demonstrated that the clearance of chronic rotavirus infection in SCID mice can be mediated by immune CD8+ T lymphocytes and that this clearance can occur in the absence of virus-specific antibodies.     

Primary murine small intestinal epithelial cells, maintained in long-term culture, are susceptible to rotavirus infection

We describe a method for long-term culture of primary small intestinal epithelial cells (IEC) from suckling mice. IEC were digested from intestinal fragments as small intact units of epithelium (organoids) by using collagenase and dispase. IEC proliferated from organoids on a basement-membrane-coated culture surface and remained viable for 3 weeks. Cultured IEC had the morphologic and functional characteristics of immature enterocytes, notably sustained expression of cytokeratin and alkaline phosphatase. Few mesenchymal cells were present in the IEC cultures. IEC were also cultured from adult BALB/c mice and expressed major histocompatibility complex (MHC) class II antigens for at least 48 h in vitro. Primary IEC supported the growth of rhesus rotavirus (RRV) to a greater extent than a murine small intestinal cell line, m-IC(cl2). Cell-culture-adapted murine rotavirus strain EDIM infected primary IEC and m-IC(cl2) cells to a lesser extent than RRV. Wild-type EDIM did not infect either cell type. Long-term culture of primary murine small intestinal epithelial cells provides a method to study (i) virus-cell interactions, (ii) the capacity of IEC to act as antigen-presenting cells using a wide variety of MHC haplotypes, and (iii) IEC biology.     

Gastroenteritis in suckling mice caused by human rotavirus can be prevented with egg yolk immunoglobulin (IgY) and treated with a protein-bound polysaccharide preparation (PSK)

Oral inoculation of human rotavirus MO strain (serotype 3) into 5-day-old BALB/c mice cause gastroenteritis characterized by diarrhea. Clinical symptoms, histopathological changes in the small intestine, and the detection of rotavirus antigen in enterocytes were all characteristic of rotavirus-induced gastroenteritis. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of immunoglobulin (IgY) from the yolks of eggs of rotavirus-immunized hens. When IgY against a rotavirus strain homotypic to the challenge virus (MO strain) was administered in the mice, complete protection against rotavirus infection was achieved. On the other hand, with oral administration of IgY against a heterotypic strain (serotype 1, Wa strain), a lower protective effect was nevertheless obtained. The four different strains of human rotavirus (Wa, KUN, MO, and ST3) were inactivated in vitro by treatment with PSK, a protein-bound polysaccharide preparation, in a dose-dependent manner. Oral administration of 2.5 mg of PSK caused a therapeutic effect on experimentally MO-infected suckling mice. The antiviral effect of PSK was indicated by the reduction of the duration of diarrhea.     

Relative Importance of Rotavirus-Specific Effector and Memory B Cells in Protection against Challenge

Adult BALB/c mice were orally inoculated with murine (strain EDIM), simian (strain RRV), or bovine (strain WC3) rotavirus. Six or 16 weeks after inoculation, mice were challenged with EDIM. At the time of challenge and in the days immediately following challenge, production of rotavirus-specific immunoglobulin A (IgA), IgG, and IgM by small intestinal lamina propria lymphocytes (LPL) was determined by fragment culture, and quantities of virus-specific antibodies at the intestinal mucosal surface were determined by intestinal lavage. Mice immunized with EDIM were completely protected against EDIM challenge both 6 and 16 weeks after immunization. Protection was associated with production of high levels of IgA by LPL and detection of virus-specific IgA at the intestinal mucosal surface. In addition, animals immunized and later challenged with EDIM did not develop a boost in antibody responses, suggesting that they were also not reinfected. We also found that in mice immunized with nonmurine rotaviruses, (i) quantities of virus-specific IgA generated following challenge were greater 16 weeks than 6 weeks after immunization, (ii) immunization enhanced the magnitude but did not hasten the onset of production of high quantities of virus-specific IgA by LPL after challenge, and (iii) immunization induced partial protection against challenge; however, protection was not associated with either production of virus-specific antibodies by LPL or detection of virus-specific antibodies at the intestinal mucosal surface.     

不同品系小鼠对实验感染念珠状链杆菌敏感性的观察

本文通过念珠状链杆菌（Ｓｔｒｅｐｔｏｂａｃｉｌｕｓｍｏｎｉｌｉｆｏｒｍｉｓ,Ｓ．ｍ．）实验感染昆明、Ｃ５７ＢＬ／６Ｊ、ＢＡＬＢ／ｃ、ＩＣＲ、ＮＩＨ、ＤＢＡ共６个品系小鼠,观察其对Ｓ．ｍ．敏感性的差异。其中昆明、Ｃ５７ＢＬ／６Ｊ两个品系在腹腔接种后表现出明显的临床、病理改变。昆明小鼠发病率和死亡率分别为９２％和８０％;Ｃ５７ＢＬ／６Ｊ分别是８０％和１２％。昆明小鼠较之Ｃ５７ＢＬ／６Ｊ小鼠起病急、病情严重,多数动物死于感染的急性期。其余品系的发病率为：ＮＩＨ８％、ＢＡＬＢ／ｃ和ＤＢＡ４％,没有动物死亡;ＩＣＲ在接种后无任何临床病理改变。在实验感染后临床病理改变方面,昆明小鼠和Ｃ５７ＢＬ／６Ｊ小鼠间有较大不同。昆明小鼠以末梢血管淤血、四肢尾部水肿、关节炎、截瘫、腹泻为主,而Ｃ５７ＢＬ／６Ｊ小鼠则以注射部位和其它部位皮下脓肿、化脓性关节炎为主。本研究提示,中国昆明小鼠对Ｓ．ｍ．敏感性最高,可以将其作为“哨兵动物”用于实验大鼠Ｓ．ｍ．的常规监测;不同品系小鼠不仅对实验感染Ｓ．ｍ．的敏感性不同,而且表现出不同的临床病理改变。     

Extramucosal spread and development of hepatitis in immunodeficient and normal mice infected with rhesus rotavirus.

The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006 and bovine rotavirus strain WC3, were evaluated in mice with severe combined immunodeficiency (SCID mice) and normal BALB/c mice. Control animals were inoculated with homologous murine strain EDIM 5099 or a tissue culture-adapted murine rotavirus. Heterologous infection with rhesus rotavirus resulted in hepatitis in 84% of SCID and 21% of BALB/c mice, with mortality rates of 27 and 0%, respectively. Surviving SCID animals developed chronic liver disease, while symptoms in BALB/c mice resolved in 2 to 4 weeks after onset. Histopathologic examination revealed a diffuse hepatitis with focal areas of parenchymal necrosis. Rotavirus was detected in liver tissue from 100% of 29 SCID and 85% (11 of 13) BALB/c animals tested by cell culture infectivity, immunofluorescence, or electron microscopy. No extramucosal spread of virus or hepatitis was observed after infection with heterologous bovine strain WC3 or homologous murine rotaviruses. This finding of a novel rotavirus-induced disease manifestation suggests altered tissue tropism in a heterologous host for a group of viruses previously shown to replicate exclusively in the gut mucosa. The implications of our observations suggest that in human vaccine trials utilizing heterologous rotavirus strains, special attention should be paid to children with immunodeficiency disorders, and screening for hepatic function should be included in vaccine protocols.