小鼠对仙台病毒Tianjin株易感性研究

研究129Sv、DBA/2、Kunming、BALB/c四种小鼠对仙台病毒Tianjin株的感染特点,并通过观察易感性的不同,确定适于研究此病毒致病性及疫苗的小型啮齿类实验动物。用9～11d龄鸡胚接种仙台病毒Tianjin株,72h后收集尿囊腔内效价为1:1 280病毒液,用5μl和6倍稀释的30μl病毒液分别接种129Sv、DBA/2、Kunming、BALB/c小鼠,观查12d小鼠体重变化,计算生存率。用6倍稀释的30μl病毒液接种Kunming、BALB/c小鼠,于接种前第1天以及接种后第4、7天断颈处死,取左肺制成切片,HE染色观察病理改变,综合判断仙台病毒Tianjin株对四种鼠感染的易感性的不同。129Sv、DBA/2小鼠在接种仙台病毒Tianjin株5μl后,最高平均体重下降分别为13.0%、4.7%,四种鼠12d生存率均为100%;接种稀释的30μl病毒液,129Sv、DBA/2、Kunming、BALB/c最高平均体重下降21.7%、30.3%、16.7%、9.6%;12d生存率分别为20%、0%、80%、100%。Kunming鼠在感染后第4、7d的肺组织病理改变较BALB/c严重,表现为大量炎细胞渗出,粘膜下层实质性增厚。以上实验结果表明DBA/2对仙台病毒Tianjin株感染最易感,BALB/c耐受性最强,易感顺序为DBA/2129SvKunmingBALB/c。DBA/2和129Sv小鼠可作为仙台病毒Tianjin株致病性及疫苗研究的首选实验动物。     

A polydactylous strain of mice

Summary A highly inbred strain ofMus musculus is described in which 12% of the males and 18% of the females are polydactylous. This polydactyly is the only abnormality occurring in these mice. In most cases only the first digit (big toe) of the right hind foot is more or less duplicated, but the left foot and other toes may also be affected. Abnormal fathers transmit the peculiarity more often to their daughters than to their sons. This fact cannot be explained on a genetic basis, since for various reasons genetic differences between these mice cannot be assumed to exist. In general, polydactylous mice have an excess number of motor neurons innervating the foot in the spinal cord on the abnormal side. This may be the cause for polydactyly as is known to be inAmphibia.     

Syngeneic mixed lymphocyte reaction in mice: strain distribution, kinetics, participating cells, and absence in NZB mice.

Co-culture of mouse spleen nonadherent (T-enriched cells with mitomycin C-treated unfractionated syngeneic spleen cells resulted in increased DNA synthesis in the responding T cells. The kinetics of this syngeneic mixed lymphocyte reaction (SMLR) showed that peak DNA synthesis occurred on day 5 of culture compared to day 4 for conventional mixed lymphocyte reaction (MLR). Anti-T cell antiserum plus complement treatment of the responding cell population abolished the reaction, and similar treatment of the stimulator population enhanced SMLR. These studies indicate that SMLR represents the response of T cells to non-T cells. Studies on the generation of cytotoxic T lymphocytes (CTL) in parallel cultures of T cells activated by syngeneic or allogeneic spleen cells showed no cytotoxicity of SMLR-activated cells for either PHA- or LPS-induced blasts but did show a good CTL response of allo-activated cells to both targets. Studies on the strain distribution of SMLR revealed that NZB mice manifested poor or no stimulation in SMLR whereas all other strains tested exhibited strong SMLR. This defect in NZB mice may be pathogenetically related to the autoimmune disease that develops in these mice.     

Sensitivity to ethanol in female mice: effects of ovariectomy and strain

Two experiments were conducted to investigate the influence of ovariectomy (OVX) on alcohol sensitivity in mice. In the first experiment, OVX, sham-operated, and nonsurgical control C57BL mice were examined for brain alcohol levels associated with alcohol-induced motor incoordination, alcohol-induced loss of righting reflex, and voluntary alcohol consumption. The second experiment employed four strains of mice (C57BL, C3H, DBA, and Swiss Webster) to evaluate the influence of OVX on alcohol-induced spontaneous activity. Taken together, the results indicated that surgical removal of the ovaries in mice does not influence alcohol-induced motor incoordination, loss of righting reflex, or spontaneous activity. Voluntary alcohol consumption, however, was affected by ovariectomy, since mice in the OVX group consumed less alcohol relative to body weight (g/kg) than controls.     

Using progenitor strain information to identify quantitative trait nucleotides in outbred mice

We have developed a fast and economical strategy for dissecting the genetic architecture of quantitative trait loci at a molecular level. The method uses two pieces of information: mapping data from crosses that involve more than two inbred strains and sequence variants in the progenitor strains within the interval containing a quantitative trait locus (QTL). By testing whether the strain distribution pattern in the progenitor strains is consistent with the observed genetic effect of the QTL we can assign a probability that any sequence variant is a quantitative trait nucleotide (QTN). It is not necessary to genotype the animals except at a skeleton of markers; the genotypes at all other polymorphisms are estimated by a multipoint analysis. We apply the method to a 4.8-Mb region on mouse chromosome 1 that contains a QTL influencing anxiety segregating in a heterogeneous stock and show that, under the assumption that a single QTN is present and lies in a region conserved between the human and mouse genomes, it is possible to reduce the number of variants likely to be the quantitative trait nucleotide from many thousands to <20.     

Biochemical studies on strain differences of mice in the susceptibility to nitrogen dioxide

Strain differences of mice in their susceptibility to nitrogen dioxide (NO₂) were examined by measuring the activities of antioxidative protective enzymes, and the amounts of antioxidants and lipid peroxides in lungs. Four strains of mice: ICR, BALB/c, ddy and C57BL/6 were used in this study and their LC₅₀ values after exposure to NO₂ for 16 hr were: 38, 49, 51 and 64 ppm, respectively (1).Genetic strain differences were observed in the enzyme activities, the antioxidant contents and lipid peroxide contents among these four different strains. The activities of glutathione peroxidase (GP_x), glutathione S-transferase, and superoxide dismutase (SOD), and the contents of non-protein sulfhydryls (NPSH), α-tocopherol (α-Toc) and total lipids in lungs of the four strains were related to their LC₅₀, while TBA reactants in lungs of the four strains were inversely related to their LC₅₀.After exposure to 20 ppm NO₂ for 16 hr, the activities of the protective enzymes and the contents of NPSH decreased, while the level of α-Toc increased markedly. The activities of GP_x, 6-phosphogluconate dehydrogenase, SOD and disulfide reductase, and the contents of NPSH, α-Toc and total lipids were also related to their LC₅₀. On the other hand, TBA reactants increased higher than those of the control groups and were inversely related to their LC₅₀.These results suggest that the protective enzymes and the antioxidants are important factors as defence mechanism in lungs to NO₂ and that the intensity of the protective systems in pigmented strains is generally greater than that in albino strains.     

Susceptibility of congenitally immunodeficient mice to a nonencapsulated strain of Cryptococcus neoformans.

The susceptibility of congenitally immunodeficient mice to a nonencapsulated strain of Cryptococcus neoformans (strain M7) was evaluated. Gnotobiotic mice with defined congenital defects in innate immunity (beige) or cell-mediated immunity (athymic) or with combined defects in innate and cellular immunity (beige athymic) were i.v. challenged with C. neoformans M7. The nonencapsulated strain of C. neoformans produced a persistent low-grade infection in the brains of all immunodeficient and immunocompetent mice used in this study. Immunocompetent mice (nu/+;bg/+) and immunodeficient bg/bg mice readily cleared nonencapsulated cryptococci from their kidneys, liver, lungs, and spleen. In contrast to nu/+ mice, nu/nu mice had a reduced capacity to clear nonencapsulated cryptococci from their kidneys and liver after i.v. challenge. Both bg/bg-nu/nu and bg/bg-nu/+ mice developed a low-grade infection in their kidneys, liver, lungs, and spleen, which was maintained throughout the 21-day study. Persistent infections were not due to reversion to an encapsulated state. These data indicate that a capsule may not always be necessary for C. neoformans to survive, in vivo, in tissues of immunodeficient and immunocompetent mice.     

Metabolic responses to leptin in obese db/db mice are strain dependent

Obese, diabetic C57BL/Ks db/db mice that lack the long-form leptin receptor exhibit no decrease in body weight or food intake when treated with leptin. Here we compared responses to leptin in two strains of db/db mice: C57BL/6J mice that are hyperglycemic and hyperinsulinemic and C57BL/Ks that are hyperglycemic and normo- or hypoinsulinemic. Chronic intraperitoneal infusion of 10 microgram leptin/day partially reversed hyperglycemia in C57BL/6J male mice but exaggerated the diabetic state of female mice. Bolus intraperitoneal injections of 40 microgram leptin/day did not effect glucose in either strain of male db/db mice, whereas chronic intraperitoneal infusion of 20 microgram leptin/day significantly reduced fasting blood glucose in male mice from both strains, especially C57BL/6J mice. Food intake, body weight, rectal temperature, and body fat did not change. Chronic intraperitoneal infusion of 10 microgram leptin/day significantly reduced body fat in lean db/+ C57BL/6J but not in C57BL/Ks mice. Thus peripherally administered leptin is active in mice that have only short-form leptin receptors, and the response is dependent on the method of leptin administration and the background strain.