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[Genetic control of antibody response to Actinobacillus actinomycetemcomitans in mice].

The purpose of this study was to determine the genetic control of the primary antibody response of inbred strains of mice against sonicated extract from Actinobacillus actinomycetemcomitans, a representative periodontal pathogen. Three groups of inbred mice strains, six independent strains, six H-2 congenic strains (B10(H-2b), B10. A (H-2a), B10. BR (H-2k), B10. D2 (H-2d), A/J (H-2a), A. BY (H-2b))nd four intra-H-2 recombinant strains (B10(Kb, I-Ak, I-E-, Db), B10. A (4R) (Kk, I-Ak, I-Eb, Db), B10. A (5R) (Kb, I-Ab, I-Ek, Dd), B10. MBR Kb, I-Ak, I-Ek, Dq] were examined on the basis of serum antibody titers to A. actinomycetemcomitans by the ELISA and of the band appearance by Western blot analysis. The levels of antibody titers varied within the first group and between A/J (H-2a) and A. BY (H-2b) in the second group. Western blot analysis showed two kinds of bands: a) constant bands appearing in all strains and b) specific bands appearing only in the distinct groups of strains. One of the latter kind of band, at 65kDa, was unique to the H-2b strains (B10, B6, A. BY) in the first and second groups and the I-Ab strains (B10 and B10. A (5R] in the third group. These results indicated that the immune response to some antigens of A. actinomycetemcomitans was influenced by the genetic background, and the immune response to some of these, such as the 65kDa antigen, was controlled by the gene in the H-2 complex.

Actinobacillus↗

Cadmium-induced elevation of hepatic isometallothionein concentrations in inbred strains of mice.

Susceptibility to Cd toxicity differs among inbred strains of mice. For example, C3H/He mice are sensitive to Cd-induced hepatotoxicity while DBA/2 mice are resistant. Metallothionein (MT), which in rodents exists predominantly as two isoproteins (MT-I and MT-II), is an important endogenous protein in the detoxication of Cd. The present investigation examines the possibility that strain-dependent susceptibility to Cd-induced liver injury is mediated by an inherited inability to accumulate a specific isoform of MT in response to Cd exposure. Hepatic concentrations of MT-I and MT-II were measured in C3H/He (Cd-sensitive) and DBA/2 (Cd-resistant) mice at various times after the administration of non-toxic (2.5 mumol Cd/kg) to hepatototoxic (80 mumol Cd/kg) dosages of Cd. The concentration of MT-I and MT-II in these strains was similar 24 h after injection of non-hepatotoxic dosages of Cd (10 mumol Cd/kg or less) as well as 6-12 h after a mildly hepatotoxic dose of Cd (20 mumol Cd/kg). The concentration of total MT in liver of Cd-sensitive mice was greater than that present in resistant mice 24-72 h after 20 mumol Cd/kg injection. The data indicates that susceptibility to Cd-induced hepatotoxicity observed in C3H/He mice is not due to a deficit in the induction of a particular isoform of MT.

Alanine Transaminase↗

Pathological changes in inbred strains of mice following early thymectomy and irradiation.

Mice subjected to thymectomy and irradiation were found to develop a range of pathological change in various organs. These changes were accompanied by antibodies to a variety of self-components. The pattern of pathological and autoimmune change was found to vary with the strain. This strain-related expression did not appear to be associated with the major histocompatibility complex (H-2).

Animals↗

Trypanosoma cruzi: flow cytometric analysis of lymphocyte subsets in susceptible and protected C3H/He mice.

Inbred strains of mice vary widely in their ability to survive infection with Trypanosoma cruzi. C3H/He mice are highly susceptible to infection with the Brazil strain T. cruzi, but can be protected by immunization with avirulent Corpus Christi strain parasites. We have examined, during the course of infection, the changes in lymphocyte populations in C3H/He mice that were infected but protected by immunization, infected but not immunized, immunized but not infected, and normal age-matched controls. Immunization- and/or infection-induced changes in lymphocyte populations in lymph nodes were unremarkable except for an increase in the percentage of Ig+ cells. Conversely, in the spleen the percentages of mu+ cells decreased and T cells increased in all manipulated animals. The increase in splenic T cell subsets in immunized only controls occurred simultaneously and thus the CD4:CD8 ratio remained similar to that of normal animals (approximately 2.2). Twenty days after infection, mice that were infected but not immunized (and thus would be expected to die 4-8 days later) showed a dramatic increase in the percentage of CD8+ cells which resulted in a decline in the CD4:CD8 ratio to 0.85. Mice protected by immunization had a CD4:CD8 ratio of 1.7 at this critical time point, which did, however, decline to 1.0 by Day 60. The percentages of all cell phenotypes examined in all mice had returned to normal levels 155 days after infection. These data suggest that alterations in the splenic CD4:CD8 ratio may be important in determining whether or not an animal can survive infection with the Brazil strain of T. cruzi.

Animals↗

Effects of methylcholanthrene and benzanthracene on blastogenesis and aryl hydrocarbon hydroxylase induction in splenic lymphocytes from three inbred strains of mice.

The effects of polycyclic aromatic hydrocarbons (PAH) such as benzanthracene (BA) and methylcholanthrene (MCA) on 3H-thymidine incorporation and aryl hydrocarbon hydroxylase (AHH) induction were assayed in mitogen-activated and non-activated splenic lymphocyte cultures derived from three strains of mice (C57BL, C3H and DBA/2). Results of three separate experiments on blastogenesis and the substrate induction of AHH were statistically significant. In mitogen-activated and non-activated lymphocytes from C57BL and C3H mice (AHH responsive strains) the percentage of blastogenesis induced by BA or MCA was higher than in lymphocytes from the non-responsive strain (DBA/2). On the basis of the PAH concentrations used MCA and BA were similar as inducers of blastogenesis and of AHH activity. AHH induction was measurable only in mitogen-activated lymphocytes and showed a non-linear relation to blastogenesis. In responsive strains, 10 microM oF BA or 1.5 microM of MCA induced AHH 2-5 fold, while in non-responsive mice induced AHH was very close to the basal level. This difference between the level of induction of lymphoblast formation and AHH in responsive and non-responsive strains of mice may be related to different subpopulations of lymphocytes in spleen or other lymphatic organs.

Animals↗

Learning in inbred mice: strain-specific abilities across three radial maze problems.

Mice belonging to the C57BL/6, DBA/2 (DBA), and C3H/He (C3H) strains were compared in three different eight-arm radial maze tasks requiring various degrees of spatial and nonspatial information processing. The results show that, on the standard radial maze task, C57 performed better than DBA, which, in turn, performed better than C3H. Fewer differences in the four-baited arm task and no difference in the cued version task were found between C57 and DBA, while C3H still performed more poorly. The high performance shown by C57 mice in all problems seems to be related to their ability to build up maze-running patterns based upon an optimal proportion of 45 degrees angle turns, according to the demand of the situation. The cognitive and discriminative mechanisms involved in the solving of each task, the sensorial characteristics of the three strains, and the limits of an approach based upon neuroanatomical-behavioral correlations are discussed.

Animals↗

Correlation between cocaine-induced locomotion and cocaine disposition in the brain among four inbred strains of mice.

BALB/cByJ, C57BL/6ByJ, CXBH/By, and CXBK/By mice differed in their locomotor response to cocaine measured 1-10 min after administration of 25 mg/kg IP of the compound. These differences were paralleled by differences in the disposition of cocaine (measured at 12 min) in the brain. Among all individual animals taken together, there was a significant correlation between locomotor stimulation and the brain concentration of cocaine. These results suggest that the differences between strains in their locomotor responsiveness to cocaine are determined, in part, by the disposition of cocaine in the brain following IP administration of cocaine.

Animals↗

Regional variations in the distribution of small intestinal intraepithelial lymphocytes in three inbred strains of mice.

The regional variation in the intraepithelial lymphocytes (IELs) in the small intestine was examined in BALB/c male and female mice and C3H/He and C57BL/6 male mice. The small intestines were taken from 11 to 12-week-old mice and divided equally into 3 parts (the proximal, middle and distal parts). IELs were isolated from each part of the intestine and analyzed with flow cytometer. The number of IELs was highest in the proximal part and lowest in the distal part. The distribution of IEL subsets was markedly different between the proximal and the distal parts, and that in the middle part showed the intermediate pattern. The percentage of alphabeta T cells were higher in the distal part. In alphabeta T cell subset, the percentage of CD8alphaalpha T cells was higher in the proximal part, whereas those of CD4 and CD4CD8alphaalpha double positive T cells were higher in the distal part. In gammadelta T cell subset, no regional variations were found. The regional variations in the number and subsets of IELs showed almost the same patterns between male and female BALB/c mice and similar patterns among three strains of mice. This strongly suggests that the regional variations in the small intestinal IELs are common to mouse species.

Animals↗

Developmental patterns of seizure susceptibility in inbred strains of mice.

Samples of mice from each of 6 inbred strains were tested for audiogenic and electroconvulsive seizures at 5 ages (14, 21, 28, 35, and 42 days). A moderately large within-strain correlation (.67) was found, indicating that developmental patterns of susceptibility to audiogenic and electroconvulsive seizures are similar within each strain. The finding of an even larger between-strain correlation (.91) indicated that strains which are highly susceptible to audiogenic seizures are also likely to be highly susceptible to electroconvulsive seizures. In a 2nd experiment, whole brain norepinephrine and serotonin were assayed in each of 5 inbred strains at 21 and 42 days of age. Results were consistent with the hypothesis that levels of these amines are inversely related to seizure susceptibility. Mice from strains which were susceptible to seizures at 21 days of age had significantly lower levels of norepinephrine and serotonin in brain than did 42-day-old, seizure-resistant animals.

Acoustic Stimulation↗

Genetic analysis of the innate immune responses in wild-derived inbred strains of mice.

The vertebrate immune system has evolved to recognize nucleic acids of bacterial and viral origin. Microbial DNA, as well as synthetic oligonucleotides based on these motifs, activates innate immune pathways mediated by the family of Toll-like receptors (TLR) initiating a cascade of signals in immune cells necessary for responses to pathogens. However, not all of the proteins that participate in TLR-mediated responses have been identified. In studies described herein, we observed significant variation in innate immune responses among selected wild-derived strains of mice. Specifically, we show that mice of MOLF/Ei, Czech/Ei, and MSM/Ms strains are hypo-responsive to polyinosinic-polycytidylic acid (poly(I:C)) because of a mutation in Tlr3. In addition, we discovered a hypo-response to cytosine guanine dinucleotide in MOLF/Ei mice and established that it is not linked to Tlr9, but to another locus. Further inquiry revealed that this hypo-response is transmitted as a monogenic dominant trait that can be mapped and cloned through positional cloning methods. These results suggest the existence of a novel molecule that can alter pro-inflammatory signals or activate additional signal transduction pathways. In addition, they support the wild-derived mouse strain as a forward genetic tool for the identification of novel immunological phenotypes.

Amino Acid Sequence↗

Cryptosporidium infections in inbred strains of mice.

Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed.

Animals↗

Genotype dependence of monoamine oxidase in inbred strains of mice.

MAO activity was found to be influenced by the genotype or strain of mouse up to 20 days of age. The strain differences observed may derive from different rates of brain development. A number of neurological mutations comprizing three pathological classes had no effect on MAO.

Age Factors↗

Immunological studies of hsv-infection of resistant and susceptible inbred strains of mice.

DBA/2 mice were found to be quite susceptible to infection with herpes simplex virus (HSV) while C57BL/6 mice and F1 hybrids between the 2 strains were relatively resistant. This difference was most marked after ip infection, but could also be demonstrated after intracerebral, intravenous or subcutaneous infection. In both strains the LD50 was considerably higher after ip infection than after iv infection, and a dose of X-irradiation was required to kill the mice by sc infection. A/J and BALB/c mice were equally susceptible after ip infection but differed significantly after iv infection. C57BL/6 were made susceptible to ip infection by immunosuppression with antilymphocyte serum or cyclophosphamide. LPS, when given simultaneously with HSV also markedly increased the susceptibility of C57BL/6 mice. Susceptible DBA/2 mice which surrvived a low dose of HSV ip were not immune but C57BL/6 mice surviving a high dose were immune against rechallenge. Both strains of mice could be protected by an apathogenic, tissue-culture-attenuated strain of HSV against infection with the virulent strain. They could also be protected by iv injection of a sublethal dose against a lethal ip infection.

Animals↗