Muscarinic receptors in brain from four strains of inbred mice

The density of brain muscarinic receptors from four strains of inbred mice was determined. C57BL/6J mice had a significantly higher density of muscarinic receptors in the forebrain than Balb/cJ or C57BL/10J mice. In the midbrain, C57BL/6J mice also had the highest density of receptors and in the hindbrain, C57BL/6J and AKR/J mice had a two fold higher receptor density compared to the other two strains. These findings demonstrate that inbred strains of mice which exhibit a range of genetically-determined behaviors, have varying densities of muscarinic receptors.     

Variation in erythrocyte purine metabolism among mouse strains

Erythrocytes of five strains of mice had ATP concentrations of ca 2.7 mumol/ml packed cells, while those of CBA mice were 23% lower, and those of BALB/C mice were 40% lower. The ratio of the concentrations of ATP and GTP were ca 3.3 in four strains but greater than 27 in three other strains. When erythrocytes from different mouse strains were incubated with radioactive precursors, appreciable strain differences were found in the apparent activities of adenine and hypoxanthine-guanine phosphoribosyltransferase, adenosine kinase, adenosine deaminase, guanine deaminase and xanthine oxidase. The activities of adenosine deaminase and guanine deaminase in sera of mice of different strains also varied.     

Comparison of sensitization to crude and purified house dust mite allergens in inbred mice

To establish a murine model for house dust mite allergy to purified mite allergens, we studied the immune response to two major mite allergens, native Dermatophagoides farinae 1 (nDer f 1) and recombinant Der f 2 (rDer f 2), and crude mite extract in four mouse strains, A/J, BALB/c, C57BL/6, and C3H/He. Mice were immunized with mite extract, nDer f 1 or rDer f 2, three times at 2-week intervals. Then mice were examined to determine status of sensitization to the antigen. Anti-mite extract IgE production was induced in all strains, and plasma IgE concentration did not differ much among the four strains. In contrast, IgE response to nDer f 1 and rDer f 2 indicated an intra-strain difference. The A/J mice had high responses to both antigens, whereas BALB/c did not respond to rDer f 2. The C57BL/6 and C3H/He mice had moderate to low IgE responses to nDer f 1 and rDer f 2. Immediate airway constriction was provoked by inhalation of mite extract or rDer f 2 in sensitized mice, and the degree of the immediate response was almost proportional to antigen-specific IgE concentration. We concluded that immunization of inbred mice with nDer f 1 and rDer f 2 achieved sensitization to mite allergens. Among the four strains, A/J mice with H-2a haplotype were the highest responder to mite allergens.     

Recovery of viable but non-culturable Campylobacter jejuni.

Suspensions of Campylobacter jejuni became non-culturable after storage in sterilized pond water at 4 degrees C for periods between 18 and 28 d, depending on the strain. Suspensions of four strains of C. jejuni that had been in water for 6 weeks, and shown to be non-culturable, were fed to suckling mice. Colonization of mice was established with two of the strains and failed with the other two strains. Examination of these suspensions under the electron microscope showed some cocci having the appearance of being viable, but most cocci and all remaining spiral forms showed extensive degeneration. The results indicate that non-culturable coccal forms of C. jejuni are capable of infecting mice but that this property may differ between strains.     

野生TW近交系小鼠主要生理指标

目的建立野生来源TW（Tianjin Wild,TW）近交系小鼠的主要生理、血常规等指标。方法分别选用F28和F29代TW近交系成年雄性小鼠25只,雌性小鼠31只,检测动物的主要生理、血常规指标。结果TW小鼠体重雌雄差异无显著性,脏器指标中雌雄性比较仅肾脏重量、肾脏系数差异有显著性（P〈0.05）;血常规检测指标中,雌雄小鼠在WBC、MCV、MCH、PLT、MONO等5项指标的均值比较差异具有显著性,其他各项均无差别。与ICR、KM、NIH及BALB/c等通用实验小鼠指标比较,TW小鼠的脾脏、脾脏系数和血小板均高于或多倍高于这些通用小鼠品系。结论TW小鼠在一些主要生理指标上与通用实验小鼠品系不同,呈现自身特点。     

Genetic variation in mouse apolipoprotein A-IV due to insertion and deletion in a region of tandem repeats.

We have detected three unique apolipoprotein A-IV (apoA-IV) charge isoforms in strains of commensal mice. The cDNA sequences for one representative of each isoform (Mus domestesticus strains C57BL/6J and 129/J and Mus castaneus) revealed a polymorphism within a series of four imperfect repeats encoding the sequence Glu-Gln-Ala/Val-Gln. Insertions or deletions of 12 nucleotides within this repetitive region have given rise to three genotypes characterized by three (129), four (C57BL/6), or five (M. castaneus) copies of the repeat unit. To ascertain the extent of this variation among other species of the Mus genus, we sequenced this region of apoA-IV cDNAs from eight additional M. domesticus inbred strains and from five wild-derived Mus species. All eight additional M. domesticus strains examined had four repeat units, as found in C57BL/6. Among wild-derived mice, however, one species (Mus spretus) had three repeats, two species (Mus cookii and Mus cervicolor) had four repeats, and two species (Mus hortulanus and Mus minutoides) had five repeats. A lack of correlation between the number of repeat units and the phylogeny of Mus species indicates that independent mutations may have occurred throughout the evolution of specific mouse lineages. We suggest that the repetitive nature of the polymorphic sequence may predispose this region to slippage errors during DNA replication, resulting in frequent deletion/insertion mutations.     

Investigation of specific substitutions in virulence genes characterizing phenotypic groups of low-virulence field strains of Listeria monocytogenes

Several models have shown that virulence varies from one strain of Listeria monocytogenes to another, but little is known about the cause of low virulence. Twenty-six field L. monocytogenes strains were shown to be of low virulence in a plaque-forming assay and in a subcutaneous inoculation test in mice. Using the results of cell infection assays and phospholipase activities, the low-virulence strains were assigned to one of four groups by cluster analysis and then virulence-related genes were sequenced. Group I included 11 strains that did not enter cells and had no phospholipase activity. These strains exhibited a mutated PrfA; eight strains had a single amino acid substitution, PrfAK220T, and the other three had a truncated PrfA, PrfADelta174-237. These genetic modifications could explain the low virulence of group I strains, since mutated PrfA proteins were inactive. Group II and III strains entered cells but did not form plaques. Group II strains had low phosphatidylcholine phospholipase C activity, whereas group III strains had low phosphatidylinositol phospholipase C activity. Several substitutions were observed for five out of six group III strains in the plcA gene and for one out of three group II strains in the plcB gene. Group IV strains poorly colonized spleens of mice and were practically indistinguishable from fully virulent strains on the basis of the above-mentioned in vitro criteria. These results demonstrate a relationship between the phenotypic classification and the genotypic modifications for at least group I and III strains and suggest a common evolution of these strains within a group.     

不同地区分离的霍乱0139菌株交叉保护力试验

本文对得自不同地区的四株０１３９菌株做了毒力、免疫力及交叉免疫力试验;四个地区０１３９菌株免疫小鼠后血清ＩｇＧ、肠液ｓＩｇＡ抗体滴度的比较以及０１群霍乱与０１３９型霍乱的交叉保护力试验。结果表明：０１群霍乱与０１３９型霍乱无交叉免疫力。０１群霍乱菌苗对０１３９型霍乱弧菌基本无保护作用;四株菌株的自身毒力基本相同。３＃株免疫力高于其它株,用３＃株免疫后能抵抗２＃、３＃及５＃株的感染。四株菌株免疫小鼠     

Antitumour activities of levans produced by Zymomonas mobilis strains

Levans produced by four Zymomonas mobilis strains showed antitumour activity against sarcoma 180 and Ehrlich carcinoma in Swiss albino mice. Levans from two strains (ZAP and CP4) had the highest effects. NMR analysis showed that the polymers were composed only of fructose units. The results suggested that the antineoplasic effect is associated to the polysaccharide molecular weight and that a particular molecular weight range may be responsible for this effect.     

不同品系小鼠对炭疽芽胞杆菌弱毒株芽胞的敏感性研究

通过比较四种品系小鼠对炭疽芽胞杆菌（Bacillus anthracis）（简称炭疽杆菌）弱毒株芽胞的敏感性，确定炭疽杆菌弱毒株芽胞攻毒合适的动物模型。采用炭疽杆菌弱毒株A16Q1（pXO1-、pXO2+）和A16PI2（pXO1+、pXO2-）的芽胞对四种品系小鼠（DBA/2、KM、ICR和BALB/c）进行腹腔攻毒，记录小鼠死亡时间，计算LD₅₀、绘制存活曲线并统计分析。运用较敏感的KM小鼠研究不同canSNP基因型毒素缺陷株（含pXO2拷贝数不同）芽胞的毒力差异。利用更为敏感的DBA/2小鼠评价S-层蛋白BA3338对荚膜缺陷株芽胞毒力的影响。结果表明，在四种品系小鼠中，毒素缺陷株芽胞的毒力均高于荚膜缺陷株芽胞的毒力。DBA/2小鼠对炭疽杆菌弱毒株芽胞的剂量依赖关系最好，最为敏感，其次是KM小鼠，而ICR小鼠和BALB/c小鼠对炭疽杆菌弱毒株芽胞不敏感。确定了DBA/2小鼠和KM小鼠在炭疽杆菌弱毒株芽胞研究中的适用性。使用KM小鼠评价了不同canSNP基因型炭疽杆菌芽胞的毒力差异，结果表明，不同canSNP基因型炭疽杆菌由于所含pXO2质粒拷贝数的差异导致芽胞的毒力不同。使用DBA/2小鼠评价了S-层蛋白BA3338缺失对炭疽杆菌芽胞毒力的影响，表明BA3338基因的缺失导致炭疽杆菌芽胞毒力降低。     

甲型H1N1流感病毒感染不同免疫缺陷小鼠的比较

目的宿主免疫系统的功能状态在病毒的感染中起着至关重要的作用,本实验观察了不同免疫缺陷小鼠感染甲型H1N1流感病毒的差异。方法使用六个品系的近交系小鼠,经乙醚麻醉后进行滴鼻攻毒,分析其在病毒感染后存活率、体重变化和肺组织病理改变的异同。结果感染H1N1病毒的6种小鼠在观察的14d内,野生型的C57BL／6小鼠感染开始体重缓慢下降,感染后期有所回升,有半数存活;BALB／c小鼠和四种免疫缺陷品系小鼠感染病毒后体重随病情发展快速下降,死亡率均为100％。野生型C57BL／6小鼠感染初期为较弥漫的间质性肺炎,后期病变逐渐局限;BALB／c小鼠和四种免疫缺陷品系小鼠感染病毒后出现弥漫的中重度间质性肺炎,细支气管上皮有变性坏死,但炎症细胞明显少于C57BL／6小鼠。结论在甲型H1N1流感病毒的初次感染中固有免疫和特异性免疫分别在感染的初期和后期起主要作用,宿主免疫系统的功能状态影响着甲型H1N1病毒感染和预后。     

Correlation between the virulence ofFrancisella tularensis in experimental mice and its acriflavine reaction

Correlation between the virulence of Francisella tularensis in experimental mice and its acriflavine reaction was studied. The cultures derived from all four strains (Ebina, CMB2, Schu, and N9) that had long been subcultured on agar media yielded two types of colonies, i.e., acriflavine reaction-positive (acf+) and acriflavine reaction-negative (acf-) colonies. All acf+ colonies, regardless of their parent strains, were shown to be low virulent in mice. Acf- colonies were shown to be either high (Ebina, CMB2) or low (Schu, N9) virulent. The low-virulent acf- colonies gained virulence during several passages in mice, whereas the acf+ colonies remained low virulent even after the animal passages.     

cis-acting determinants of basal and lipid-regulated apolipoprotein A-IV expression in mice

The levels of apolipoprotein A-IV (apoA-IV) mRNA are regulated by dietary lipid in the liver of both the mouse and rat. Thirteen different inbred mouse strains were fed a high lipid diet, and the effect on apoA-IV liver mRNA levels was examined. It was found that each strain responded in one of two ways. Mice of four strains had higher liver apoA-IV mRNA levels as compared with syngeneic mice fed a normal chow diet. Mice of the other nine strains had decreased liver apoA-IV mRNA levels as compared with syngeneic mice fed a normal chow diet. Using F1 hybrids between mice from BALB/c, C3H, and C57BL/6 and between 129 and C57BL/6, as well as recombinant inbred strains derived from a cross between BALB/c and C57BL/6, we have shown that both the normal level of liver apoA-IV mRNA in the chow-fed mice and the lipid-dependent regulation of apoA-IV mRNA levels are controlled by cis-acting genetic elements. The apoA-IV mRNA levels in mice fed a normal diet varied dramatically among strains, with the largest difference (90-fold) being between the 129/J inbred strain and the C57BL/6J strain. In addition, we have examined the expression of apoA-IV during mouse development. ApoA-IV mRNA is expressed early in mouse liver (16 days postcoitum), whereas others have shown previously that rat liver apoA-IV mRNA is undetectable until 14 days after birth. ApoA-IV mRNA levels in the intestine and apoA-I mRNA levels in the liver and intestine, by contrast, mirror the pattern seen in the rat.     

Lupus-prone mice have an abnormal response to thioglycolate and an impaired clearance of apoptotic cells

Deficiency of complement in humans and mice is associated with the development of lupus and with abnormal repair of inflammatory and immune complex-mediated tissue injury. Here we ask whether similar defects in the resolution of inflammation are found in mice prone to spontaneous lupus. We compared the response to an i.p. injection of thioglycolate between two lupus-prone strains (MRL/Mp and NZB/W) and two non lupus-prone strains of mice (C57BL/6 and BALB/c). In all four strains the influx of polymorphonuclear neutrophils (PMN) was similar. However, by 96 h clearance of PMN in the control strains was complete, whereas in the autoimmune-prone strains PMN were still detectable. The number of mononuclear cells recruited was markedly reduced in the lupus-prone strains compared with the controls, and their phenotype was different. The lupus-prone strains had significantly fewer elicited macrophages that were CD11b-high and Ly6C-negative. In lupus-prone mice at 24 h there was a significantly increased number of apoptotic PMN free in the peritoneum, accompanied by a reduced percentage of macrophages containing apoptotic bodies, suggesting a defect in their uptake. An impaired ability of resident peritoneal macrophages from lupus-prone mice to engulf apoptotic cells was demonstrated by in vivo and in vitro cell clearance assays. These observations indicate that lupus-prone strains have an abnormal inflammatory response to thioglycolate and an intrinsic impairment in apoptotic cell uptake. These findings have implications for the initiation of autoimmunity, as lupus autoantigens are expressed on dying cells, and impaired disposal of these could enhance the development of autoimmunity.     

Sex and strain differences in the hepatotoxic response to acute cocaine administration in the mouse

Cocaine-induced hepatotoxicity was examined in vivo in a dose-responsive manner in C57BL/6Ibg, DBA/2Ibg, C3H/2Ibg, and Balb/cJ mice. Serum glutamic-pyruvic transaminase (SGPT) activities were determined 24 hours after intraperitoneal (IP) administration of cocaine (20 to 100 mg/kg). Significant elevations (100- to 150-fold) in SGPT were observed in male mice receiving cocaine. Significant differences in sensitivity to cocaine-induced hepatotoxicity were found among males of the inbred strains, with Balb being most sensitive and C57BL being least sensitive and C3H and DBA strains exhibiting intermediate sensitivity. Female mice of the four inbred strains were more resistant than males to cocainemediated hepatotoxicity, as indicated by only twofold to tenfold elevations in SGPT values. Among the females, sensitivity of the four inbred strains—as indicated by dose response curves—fell into two categories: the sensitive strains (C3H and C57BL) and the resistant strains (Balb and DBA). Pretreatment of males of the four inbred strains with the P-450 inducer phenobarbital resulted in enhancement of cocaine-mediated hepatotoxicity in the C57BL and Balb but not the C3H and DBA mice. Phenobarbital pretreatment of females of the four inbred strains resulted in enhancement of the hepatotoxic response to cocaine in the C3H, DBA, and Balb mice. Phenobarbital-pretreated C57BL females exhibited a 100% mortality rate after the acute cocaine dose, and thus no determination of hepatotoxicity could be established for them. These data demonstrate sex and strain differences in cocaine-induced hepatotoxicity and suggest that phenobarbital pretreatment does not uniformly enhance the hepatotoxicity of cocaine.     

Evidence for the Asiatic origin of endogenous AKR-type murine leukemia proviruses.

A restriction endonuclease cleavage map of the genome of AKV, the endogenous, ecotropic leukemia virus of AKR mice, has been derived. By using this map and analyzing DNA from congenic mice, we have defined four DNA fragments diagnostic for AKV proviruses. Analysis of DNAs from 10 strains of American laboratory mice revealed that all strains carrying inducible, ecotropic murine leukemia viruses yielded DNAs which contained the four DNA fragments diagnostic for AKV. Virus-negative strains lacked these fragments in their DNA. Screening DNA from 23 additional mice revealed that, among these mice, only mice from Asia gave rise to the DNA fragments diagnostic of an AKV provirus. We conclude that all of the endogenous ecotropic murine leukemia proviruses in American laboratory mice are closely related since they share a common set of restriction endonuclease cleavage sites. These proviruses appear to derive from the East Asian ancestors of these mouse strains. Analysis of DNA from six selected mice with an additional restriction endonuclease showed that greater than 97% of the nucleotide sequences in each provirus are contigous and that these endogenous proviruses are indistinguishable from proviruses introduced by exogenous infection.     

A comparison of phospholipase activity, cellular adherence and pathogenicity of yeasts

Phospholipase A and lysophospholipase activities were measured in the culture fluid and in the blastospores of Candida albicans. When phospholipase activity was measured in six yeasts (four strains of C. albicans and a single strain each of Candida parapsilosis and Saccharomyces cerevisiae) a correlation was found between this activity and two potential parameters of pathogenicity. The C. albicans isolates which adhered most strongly to buccal epithelial cells and were most pathogenic in mice had the highest phospholipase activities. Non-pathogenic yeasts, including C. albicans isolates which did not adhere and did not kill mice, had lower phospholipase activities.     

昆明小鼠4个可能近交系的基因分型验证

在我国,昆明小鼠作为一种实验动物广泛应用于药理和遗传学相关的研究领域。但由于昆明小鼠属于远交群,而且不同地区的种群间已经出现了严重分化,缺乏具有显著特征的近交系,这使得它在生物学上的应用受到了很大的限制。研究人员已经以昆明小鼠为背景培育出了几个可能的近交系,但由于缺乏可靠的遗传检测,至今未得到广泛的认可和应用。文章收集昆明小鼠的4个已经60代以上兄妹交配繁殖的可能近交系,并以两个标准近交系BALB/c和C57BL/6为参照,利用30个微卫星标记对每个品系的5只小鼠进行了微卫星基因分型,进而分析其遗传纯度。结果发现,品系A1和品系N4在本研究所用的30个位点均呈纯合状态;而T2和N2均在D15Mit16位点呈杂合状态。本研究第一次为我国昆明小鼠近交系的遗传学纯度提供了可靠的分子水平证据。今后应当加强昆明小鼠近交系的标准化,以扩大其在遗传学方面的应用。     

Heterogeneity in the CD200R paired receptor family

Paired receptors are groups of closely related membrane proteins that have the potential to either inhibit or activate. The CD200R family consists of one inhibitory member, CD200R and various numbers of activating genes according to species with three defined in C57BL/6 mice. A genomic PCR strategy was used to examine the repertoire of genes in both laboratory and wild-derived mice. Most mouse strains tested (18/22) had three activating genes, and 16 of these had either the combination of CD200RLa, Lb, and Lc or CD200RLa, Lb, and Le. The Lc and Le genes were mutually exclusive and were equally common (10 strains). Wild-derived mice varied more with one example of strains with one, two, and four activating genes. An inhibitory CD200R gene was detected in each mouse strain, although two slightly different sequences were found in both laboratory and wild-derived mice. This diversity is probably being driven by pathogens but is less extensive than for many NK paired receptors such as KIR and Ly49. It is possible that myeloid paired receptors are involved in immune regulation of responses against pathogens rather than directly killing infected cells as for NK cells and, hence, under less intense evolutionary pressure.     

Hippocampal commissure defects in crosses of four inbred mouse strains with absent corpus callosum

It is known that four common inbred mouse strains show defects of the forebrain commissures. The BALB/cJ strain has a low frequency of abnormally small corpus callosum, whereas the 129 strains have many animals with deficient corpus callosum. The I/LnJ and BTBR T+ tf/J strains never have a corpus callosum, whereas half of I/LnJ and almost all BTBR show severely reduced size of the hippocampal commissure. Certain F1 hybrid crosses among these strains are known to be less severely abnormal than the inbred parents, suggesting that the parent strains have different genetic causes of commissure defects. In this study, all hybrid crosses among the four strains were investigated. The BTBR × I/Ln hybrid expressed almost no defects of the hippocampal commissure, unlike its inbred parent strains. Numerous three‐way crosses among the four strains yielded many mice with no corpus callosum and severely reduced hippocampal commissure, which shows that the phenotypic defect can result from several different combinations of genetic alleles. The F2 and F3 hybrid crosses of BTBR and I/LnJ had almost 100% absence of the corpus callosum but about 50% frequency of deficient hippocampal commissure. The four‐way hybrid cross among all four abnormal strains involved highly fertile parents and yielded a very wide phenotypic range of defects from almost no hippocampal commissure to totally normal forebrain commissures. The F2 and F3 crosses as well as the four‐way cross provide excellent material for studies of genetic linkage and behavioral consequences of commissure defects.