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Ethanol intoxication as a function of genotype dependent responses in three inbred mice strains.

Three strains of mice, ICR Swiss, DBA/2J and C57Bl/6J were compared for initial sensitivity, recovery from intoxication, and acute tolerance development to ethanol. The The C57Bl/6J mice were found to be less sensitive and to recover more rapidly from the effects of the same dose of ethanol than the other two strains treated. None of the strains tested demonstrated acute tolerance to ethanol when given the same dose 3 hours later.

Alcoholism↗

Induction of tumor necrosis factor alpha by Leishmania infantum in murine macrophages from different inbred mice strains.

The present study was undertaken to determine whether the viscerotropic species, Leishmania infantum, endemic in Italy, could induce tumor necrosis factor alpha (TNF alpha) in murine macrophages. Genetically susceptible (Lshs) and resistant (Lshr) mice were used in the attempt to correlate TNF alpha production with the ability to control parasite growth and replication. Resident peritoneal macrophages of C3H/HeN, DBA/2, CBA (Lshr), C57BL/10 and BALB/c (Lshs) mice were infected in vitro with promastigotes at a parasite to cell ratio of 8:1. No significant differences in the percentages of infected peritoneal cells of Lshs versus Lshr mice were observed until 72 h of in vitro culture. On the contrary, Kupffer cells from Lshr mice inhibited Leishmania replication. Peritoneal macrophages of resistant mice produced significantly higher amounts of TNF alpha as compared to susceptible mice. TNF alpha production of both resistant and susceptible mice peaked at about 5 h after the challenge with the parasite. No TNF alpha was found in supernatants of infected Kupffer cells from all the strains tested. The ability of macrophages from susceptible or resistant mice strains to produce TNF alpha after challenge with Leishmania infantum does not seem related to their capacity to control parasite replication in vitro.

Animals↗

[The level of sex steroids in the blood of inbred-strain mice during a normal pregnancy and after zygote retransplantation].

The effect of genotypes on the blood content of progesterone and estradiol was studied in female CBA, C57BL and BALB mice. We also studied progesterone content at the early stages of pregnancy after the effect of stress factors, such as narcosis and surgery, involved in the retransplantation of the embryo from the donor to the recipient. The levels of sex hormones increased during pregnancy with two peaks on the 6-8th and 14-18th days. The pattern of changes in the level of both hormones depends on the female genotype: at some stages, reliable interstrain changes in the blood content of both progesterone and estradiol were found. At the same time, narcosis and bilateral laparotomy did not affect the blood level of progesterone within 12 h after mating, despite marked activation of the adrenocortical system. The data obtained should be taken into account when selecting mother-fetus pairs for retransplantation of embryos in experimental and farm animals.

Animals↗

Quantitative morphological analysis of hippocampal structures in DBA1 and DBA2 inbred mice strains with genetically determined different shuttle box behavior: the mossy fiber system with reference data to the C3H strain.

The present work deals with morphological aspects which are likely related to a genetically determined learning behavior in the shuttle box paradigm. Subregions of the hippocampal mossy fiber system in two closely related inbred mice strains, DBA1 as a bad active avoider and DBA2 as a good one, are compared. Additionally, data derived from C3H (bad active avoider) studies are analyzed. Beside of certain structural similarities in DBA1 and DBA2 such as the elongation of infrapyramidal mossy fibers along the CA3 neurons this study pays attention to the topography of hilus and basal CA3 mossy fiber innervation.

Animals↗

Variation in susceptibility to atherosclerosis among inbred strains of mice.

Ten inbred strains of mice were fed an atherogenic diet containing 1.25% cholesterol, 0.5% cholic acid and 15% fat. The strains were examined for plasma cholesterol and triglyceride levels and for formation of lipid-containing lesions in the aortic wall. The strains differed considerably in the frequency of lesion formation after 14 weeks on the atherogenic diet with a range of 0-1.8 lesions/mouse. The order of susceptibility to lesion formation from the least susceptible to the most susceptible was BALB/cJ, C3H/J, A/J, SWR/J, NZB/J, less than 129/J, AKR/J, DBA/2J, less than C57L/J less than C57BL/6J. Total plasma cholesterol after 5 weeks on the diet varied from 131 mg/dl to 328 mg/dl among strains; however, there was little correlation between total cholesterol levels and susceptibility to lesion formation (r = 0.29). Plasma triglycerides after 5 weeks on the diet varied less than cholesterol with a range of 137-220 mg/dl. An analysis of the genetic differences among inbred strains of mice might provide useful insights into lipid metabolism and the development of atherosclerosis.

Animals↗

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.

Animals↗

Atherosclerosis and plasma and liver lipids in nine inbred strains of mice.

Nine inbred strains of mice, which are progenitors of recombinant inbred sets, were evaluated for aortic lesion formation and plasma and liver lipid levels. This survey was done to determine if a semi-synthetic high-fat diet could elicit the same extent of diet-induced atherosclerosis as that observed in mice fed a natural ingredient high-fat diet and to discover strain-specific plasma and liver lipid variants for future genetic characterization. Evaluation of aortic lesions after 18 wk of diet consumption showed that strains C57BL/6J, C57L/J, SWR/J and SM/J were susceptible to atherosclerosis and that A/J, AKR/J, C3H/HeJ, DBA/2J and SJL/J were relatively resistant. High-density lipoprotein cholesterol (HDL-C) levels were negatively correlated to lesion formation. Susceptible strains had decreased HDL-C levels when switched from chow to the semi-synthetic high-fat, high cholesterol diet, whereas resistant strains either showed no change or a slight increase in HDL-C levels. The exception to this pattern was found in SM mice, which were susceptible to aortic lesion formation but maintained the same HDL-C level on both chow and high-fat diets. HDL size differed among the strains, and levels of plasma apolipoprotein A-I and A-II correlated with HDL-C levels. Liver damage was not correlated to HDL-C levels or to susceptibility to atherosclerosis. Mice from strain A, which are resistant to atherosclerosis, had evidence of liver damage as observed by elevated levels of plasma alanine aminotransferase activity, by liver histology, by increased liver weight and by exceptionally high hepatic cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

An immunogenetic analysis of resistance to herpes simplex virus retinitis in inbred strains of mice.

Specific inbred strains of mice have been shown to vary considerably in their resistance and susceptibility to herpes simplex virus (HSV) infection. We injected 2 X 10(5) plaque forming units (PFU) of the KOS strain of HSV-1 intracamerally into one eye of BALB/c, C57Bl/6, and F1 (BALB/c X C57Bl/6) mice. HSV-1 antigens were localized in frozen sections of enucleated eyes at 10 to 14 days post-inoculation. Injected eyes of BALB/c mice showed an anterior uveitis with HSV-1 antigens in the anterior segment and an intact retina free of HSV antigens. The retina of the contralateral uninjected eye was necrotic and contained HSV-1 antigens. In both C57Bl/6 and F1 mice, HSV antigens were limited to anterior segment structures in the injected eye, whereas, in contrast to BALB/c mice, the contralateral retina appeared histologically normal and contained no viral antigens. The C57Bl/6 and F1 strains remained relatively resistant to retinal infection even if pretreated with up to 800 Rads of irradiation. The retinas of normal or sublethally irradiated C57Bl/6 and F1, but not BALB/c strains, were also resistant to intravitreal injection of HSV. These results suggest that resistance to HSV retinitis is a dominantly inherited trait, which depends only partly upon immunologic factors and may be heavily influenced by the inherent ability of host cells from different murine strains to support a productive viral infection.

Animals↗

Relationship between brain cortex and testis maturation rate in two inbred strains of mice.

Two inbred strains of mice, SEC/1ReJ (SEC) and C57BL/6J (C57) showed significant differences in the maturation rate of two different anatomical districts: the brain cortex and the seminiferous epithelium. The cortical maturation rate, recorded by means of an electrocorticogram (ECoG), indicated that SEC mice are slower in the development of an adult wave pattern than C57 mice, which are more mature at birth. Furthermore, the C57 strain appears to have a faster maturation rate of the seminiferous epithelium. In fact, spermatogenesis in these mice shows the presence of spermatids in the seminiferous epithelium at 25 days, and mature spermatozoa in the epididymis at 40 days. Instead, the SEC strain, because of its slower development, shows a considerable delay of spermiogenesis and the epididymis is still empty at 40 days. These data, together with those on the ECoG differences of these strains, seem to indicate a relationship between brain and testis maturation.

Animals↗

Neuropathology of experimental allergic encephalomyelitis in inbred strains of mice.

Ten inbred strains of mice were tested for their susceptibility to experimental allergic encephalomyelitis (EAE) after sensitization with mouse spinal cord in complete Freund's adjuvant followed by booster injections of Bordetella pertussis. The results extended previous findings in that not all susceptible mice possessed the H-2s haplotype, but mice with an H-2q background (DBA1/J strain) were also susceptible. Neuropathologic examination of experimental allergic encephalomyelitis in the mouse showed that from strain to strain, the condition was similar. The over-all pathologic picture was somewhat midway between that seen in other species sensitized with whole nervous tissue in complex Freund's adjuvant and hyperacute experimental allergic encephalomyelitis in rats similarly sensitized but with the addition of B. pertussis. Perivascular cuffing, though present, was less pronounced than in other species. There was a prominent polymorphonuclear response, and extravasation of fibrin and red cells occurred. Primary demyelination was a transient, early feature of the disease process in mice, but nerve fiber depletion and gliosis occurred as the disease progressed. The observed myelin degradation most commonly involved the ingestion by macrophages of small fragments of dissociated myelin via crypts or infoldings of the cell surface, at the bases of which were pinocytic, coated vesicles. A similar pattern of myelin breakdown has been described in mouse hepatitis virus encephalomyelitis and multiple sclerosis.

Animals↗

The virulence of Trypanosoma congolense can be determined by the antibody response of inbred strains of mice.

Three inbred strains of mice, BALB/c, C57Bl/6 and CBA/J were infected with three clones of Trypanosoma congolense, DIND/3.1, SAM/28.1 and KAR/57.1, which were obtained from three different stocks. DIND/3.1 was of high virulence for BALB/c and CBA/J but of negligible virulence for C57Bl/6. SAM/28.1 was of high virulence and KAR/57.1 of negligible virulence for the three strains of mice. In each case, high virulence was correlated with a late, transient and low titre protective antibody response measured by complement mediated lysis of live organisms. Negligible virulence was correlated with an early, high titre protective antibody response. Suppression of the antibody response by sub-lethal irradiation or cyclophosphamide treatment of the host turned a trypanosome infection of negligible virulence into one of high virulence. In mice with mixed infections it was shown that highly virulent trypanosomes did not influence the course of infection and antibody response to trypanosomes of negligible virulence and vice-versa. The relationship of total antigen mass to the kinetics of the antibody response suggests that 1000- to 10,000-fold less antigen is required in good responder than in bad responder mice to trigger the immune response. Thus the virulence of T. congolense can be determined by the antibody response of inbred strains of mice. The specificity and dose dependency of this antibody response seem to implicate the involvement of Ir genes.

Animals↗

Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice.

The inbred strains of mice C57BL/6J (B6) and C3H/HeJ (C3H) have very different femoral peak bone densities and may serve as models for studying the genetic regulation of bone mass. Our objective was to further define the bone biomechanics and microstructure of these two inbred strains. Microarchitecture of the proximal femur, femoral midshaft, and lumbar vertebrae were evaluated in three dimensions using microcomputed tomography (microCT) with an isotropic voxel size of 17 microm. Mineralization of the distal femur was determined using quantitative back-scatter electron (BSE) imaging. MicroCT images suggested that C3H mice had thicker femoral and vertebral cortices compared with B6. The C3H bone tissue also was more highly mineralized. However, C3H mice had few trabeculae in the vertebral bodies, femoral neck, and greater trochanter. The trabecular number (Tb.N) in the C3H vertebral bodies was about half of that in B6 vertebrae (2.8(-1) +/- 0.1 mm(-1) vs. 5.1(-1) +/- 0.2 mm(-1); p < 0.0001). The thick, more highly mineralized femoral cortex of C3H mice resulted in greater bending strength of the femoral diaphysis (62.1 +/- 1.2N vs. 27.4 +/- 0.5N, p < 0.0001). In contrast, strengths of the lumbar vertebra were not significantly different between inbred strains (p = 0.5), presumably because the thicker cortices were combined with inferior trabecular structure in the vertebrae of C3H mice. These results indicate that C3H mice benefit from alleles that enhance femoral strength but paradoxically are deficient in trabecular bone structure in the lumbar vertebrae.

Animals↗

Emotionality, exploratory behavior, and locomotion in aging inbred strains of mice.

Two inbred strains of mice, C57BL/6J and DBA/2J, ranging in age from 2 to 38 months, were tested in an open field using the free exploration method. Scores were obtained for locomotor activity, exploratory behavior and emotionality. Strain differences were observed for all three variables. Beginning at late maturity (12 months), locomotor activity decreased with increasing age. Exploratory behavior was at a low level for DBA/2J mice at all ages. For C57BL/6J mice, exploratory behavior decreased significantly between 2 and 6 months and remained stable thereafter. Emotionality remained unchanged with advancing age for both strains of mice.

Aging↗

Colony-stimulating factors increase resistance to atypical mycobacteria in resistant mice, whereas they decrease resistance in susceptible strains of mice.

Inbred strains of mice, notably the susceptible C57BL/6 and the resistant A/J strains of mice, were infected with a strain of Mycobacterium evium. The infection in the visceral organs of mice was then studied, and the effect of colony-stimulating factors, i.e., interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (CSF-1) on the infectious process was evaluated. Infusion of GM-CSF, CSF-1, and IL-3 led to a significant, albeit rather modest, increase in the mycobacterial resistance of A/J mice, as seen by a decrease in the number of colony-forming units (CFU) in the organs. Conversely, these CSFs dramatically increased the susceptibility of C57BL/6 mice, as seen by increased bacterial numbers in the spleens and livers. In vitro studies demonstrated that resident peritoneal macrophages from susceptible mice were more permissive than cells from resistant mice for mycobacterial growth. Application of CSFs on peritoneal macrophage monolayers led to an increased growth in both A/J and C57BL/6 monolayers for IL-3 and CSF-1 and a small microbiostatic effect for GM-CSF. Cytokine treatment did not, however, change the resistance/susceptibility phenotype of isolated macrophages. Our results indicate that CSFs may exert beneficial or detrimental effects on resistance to mycobacteria depending on the host genetic make up.

Animals↗

Genetic variation in brain L-glutamate decarboxylase activity from two inbred strains of mice.

Two inbred strains of mice, C57BL/6Bg and DBA/1Bg, were compared for genetic varaition in brain L-glutamate decarboxylase (GAD) activity. Although no large difference was found between the strains in whole brain GAD activity at adult age (27--45 days postnatally), regional examination revealed a difference in GAD activity in the cerebral cortex (15% higher in DBA); subcellular examination revealed a difference in synaptosomal fraction (21% higher in DBA). When GAD activity was measured in synaptosomal fractions prepared from dissected cerebral cortex, DBA was 34% higher than C57BL. In addition, differences in GAD activity between the two strains could be observed even in the whole brain (10--15% higher in DBA) during earlier development (15--23 days postnatally). These data indicate that at adult age, genetic difference in GAD activity between the two strains exists mainly in nerve terminals of the cerebral cortex. It is postulated that the difference may be due to a genetically mediated mechanism regulating GAD in the presynaptic terminals of GABA neurons of the cerebral cortex.

Age Factors↗