BALB/c and C57BL/6 mouse strains influence gastric function outcomes with administration of cisplatin and dexamethasone

Abstract Our aim was to evaluate the effects of cisplatin and dexamethasone alone and combined on gastric contractility and histomorphometry of BALB/c and C57BL/6 mice. BALB/c and C57BL/6 male mice (8-week-old) were randomly separated into: Control; Cisplatin (7.5 mg/Kg); Dexamethasone (2.0 mg/Kg); and Dexamethasone plus Cisplatin (2.0 mg/Kg of dexamethasone 1-hour prior to 7.5 mg/Kg of cisplatin). Drugs were administered intraperitoneally for three days. Body weight and food intake were evaluated on 2nd day. Alternating Current Biosusceptometry technique was employed to measure gastric contractions on 3rd day. Afterward, mice were killed for gastric histomorphometric analysis. Cisplatin decreased food intake and caused bradygastria in BALB/c mice; however, the amplitude of gastric contractions decreased in both BALB/c and C57BL/6. Dexamethasone and cisplatin combined restored the gastric frequency and food intake only in BALB/c, but drug combination reduced the gastric amplitude of contractions in both strains. Dexamethasone alone increased gastric mucosa thickness in C57BL/6 and decreased muscular thickness in BALB/c. In conclusion, the mouse strains presented differences in acute effects of cisplatin and dexamethasone alone and combined on gastric function. This reinforces the importance of choosing the appropriate mouse strain for studying the acute effects of drugs on the gastrointestinal tract.

Age- and substrain-dependent sperm abnormalities in BALB/c mice and functional assessment of abnormal sperm by ICSI.

BACKGROUND: Male BALB/c mice produce a high proportion of morphologically abnormal sperm. Although the BALB/c male may be a useful model of human male infertility, it remains unclear whether the sperm abnormality rate (SAR) is affected by age or the BALB/c substrain. METHODS: SARs (head shape) were assessed in three BALB/c substrains (A, AnN, ByJ) at 7 and 9 weeks and 6-10 months of age (c.100 sperm/male). The functional ability of abnormal sperm produced from 7-week-old and 6-10-month-old males was determined in BALB/c AnN mice by ICSI. RESULTS: The SAR (quasi-normal plus abnormal sperm) was lower in BALB/c A than in the other two strains (P < 0.05). Further, the SARs of BALB/c AnN and ByJ strains at 7 weeks old were high and decreased rapidly by 9 weeks, suggesting that early spermatogenesis (i.e. the first wave of spermatogenesis) produced low-quality sperm. ICSI experiments indicated that 2-cell stage embryos which developed from morphologically abnormal sperm from both the first wave of spermatogenesis and the older mice (6-10 months) were similar to those from morphologically normal sperm in terms of producing progeny, although the number of 2-cell embryos was slightly lower (P < 0.05, chi(2) test) than with normal sperm. CONCLUSIONS: Although the SARs of BALB/c mice are affected by both age and substrain, the embryos that developed from morphologically abnormal sperm have normal genetic potential in terms of production of progeny.

Balb/Cj male mice do not feminize after infection with larval Taenia crassiceps.

Balb/cJ mice fail to mount an immune response capable of clearing infection with larval Taenia crassiceps. Additionally, male Balb/cJ mice display a lag in larval growth of approximately 3 wk as compared to growth in female mice. It has been reported that male Balb/ cAnN mice generate a protective immune response early in infection, and become permissive to larval growth after they feminize (200-fold increase in serum estradiol and 90% decrease in serum testosterone). To determine if a different strain of Balb/c mice (Balb/cJ) also feminize, serum was collected from infected male mice for 16 wk and levels of 17-beta-estradiol and testosterone were measured via ELISA. In addition, the mounting responses of 12- and 16-wk infected male mice, as well as uninfected control mice, were determined after isolation with a female mouse. The results of these experiments show that male Balb/cJ mice do not feminize during infection with larval T. crassiceps. There was no significant change in serum levels of either 17-beta-estradiol or testosterone during the course of infection (> 16 wk). Moreover, there was no significant decrease in the number of times infected male mice mounted the female mouse as compared to uninfected controls. These results suggest that there may be variances between the substrains of Balb/c mice that lead to the phenotypic differences reported for male Balb/cJ and Balb/cAnN mice.

[Analyzing genetic quality of BALB/c mouse strains in China by microsatellite marking].

Eleven BALB/c mouse strains of Beijing, Shanghai, Shenyang, Haerbin, Guangzhou, Chongqing and Changchun were monitored in order to assure the genetic quality of inbred BALB/c mouse strains in China and to estimate the credibility of microsatllite markers. Fourteen microsatellites loci on different chromosomes were investigated by PCR analysis. It showed that all these microsatellites DNA loci displayed single allelic gene band in mouse strains of Beijing, Shanghai and Haerbin. But the mice came from Shenyang, Guangzhou, Chongqing and Changchun had polymorphisms or heterozygosis, among which the Shenyang and Changchun strains showed polymorphisms and heterozygosis at two separate loci. Four loci showed polymorphisms or heterozygosis in one of the Guangzhou mouse strains. The Chongqing strains showed polymorphisms and heterozygosis at seven loci, including the D10Mit180 locus as compared with the Shanghai strains.

Relative immunogenicity of PorA subtypes in a multivalent Neisseria meningitidis vaccine is not dependent on presentation form.

The hexavalent meningococcal vaccine HexaMen, containing six PorAs on two vesicles, was tested in clinical studies. Although fourfold increases in serum bactericidal activity (SBA) titers against all of the PorAs were observed, there were significant differences between PorA-specific SBA titers. SBA titers were mainly directed against one PorA from each vesicle, P1.5-2,10 and P1.5-1,2-2, and were lower against the other PorAs, especially P1.7-2,4 and P1.19,15-1. We investigated whether these differences were due to immunological interference that resulted in competition between the three PorAs on the same vesicle or whether they were caused by a difference in the immunogenicities of the separate PorAs. Therefore, mice were immunized either with HexaMen, with six monovalent outer membrane vesicles (OMVs) representing the same six PorAs simultaneously (HexaMix), or with only one of the monovalent OMVs. The immunoglobulin G and SBA titers after HexaMen immunization in mice resembled the results obtained in clinical studies. Although immunization with HexaMix gave higher titers than immunization with HexaMen for some PorAs, the pattern of high and low titers was the same. Similar differences in immunogenicity between subtypes were seen after monovalent immunization when interference was eliminated as a cause of the differences. Monovalent immunization resulted in higher titers for P1.5-1,2-2 and P1.7,16 than immunization with HexaMen. However, no significant differences were found for the weakly immunogenic PorAs, P1.7-2,4 and P1.19,15-1. Since immunization with the six PorAs in the trivalent presentation form (HexaMen) and in the mixture of monovalent vesicles (HexaMix) resulted in the same pattern of high and low titers, we concluded that the differences between the PorA-specific responses are due to differences in the immunogenicities of the various PorAs and not due to interference that results in competition between different PorAs.

Experimental allergic orchitis in mice: III. Differential susceptibility and resistance among BALB/c sublines.

Significant differences in susceptibility to the induction of experimental allergic orchitis (EAO) were found to exist among the various substrains of BALB/c mice. Substrains which were susceptible to disease induction include BALB/cKa, BALB/cByJ, BALB/cWtJ, BALB/cCmcCr, BALB/cCrgl, BALB/cHeA, BALB/cAnNCr, BALB/cPt, BALB/cWehiUnm, BALB/cOrnl and BALB/cArg whereas BALB/cJ and BALB/cSki BoyPt were resistant to EAO. Aspermatogenesis and autoimmune vasitis, two additional lesions characteristic of murine EAO, were found to correlate with susceptibility to autoimmune orchitis. Susceptibility and/or disease resistance did not segregate within any of the evolutionary branches of the BALB/c genealogic tree nor did it correlate with any of the previously described allelic differences distinguishing BALB/c substrains. Therefore, differential disease susceptibility may represent the manifestation of mutational and/or retroviral induced genotypic differences in the regulatory genes controlling testicular autoimmunity.

Genetic control of the production of anti-thyroid hormone antibodies in mice immunized with human thyroglobulin.

Various strains of mice with different H-2 and Igh-I allotypes were immunized with human thyroglobulin (HTg) and genetic control of the production of anti-thyroid hormone antibodies was examined. Anti-HTg antisera obtained from different strains of mice were examined for the presence of anti-thyroid hormone antibodies. At least one Ir-gene which controls the production of anti-T4 antibodies by immunization with HTg was identified in the I-A subregion. The presence of Ir-genes outside the H-2 was also suspected. Concerning the production of anti-T3 antibodies, only three strains (B10.A, C3H.SW, BALB/cJ) were high responders and therefore we were unable to identify the Ir-gene for them. These results indicate the presence of Ir-gene which controls the immune response in mice against thyroid hormone and suggest that the anti-thyroid hormone antibodies observed in various thyroidal and non-thyroidal disorders could be anti-HTg antibodies. The significance of genetic control of the production of anti-thyroid hormone antibodies in mice immunized with HTg is discussed.

Serological analysis of H-2 antigens expression on the cell surface of selected mouse tumors.

Studies on histocompatibility antigens expression on different selected mouse tumor cells revealed very variable pattern. No qualitative alterations in H-2 antigens expression on the cells of the following tumors: RL male 1 and MP26a of BALB/c (H-2d) mice, ASL-1 and RADA-1 of A (H-2a) mice, EL-4 and E male G2 of C57B1/6 (H-2b) mice, K36 and AKSL-4 of AKR (H-2k) mice could be detected. However, the quantitative differences in H-2 antigens expression on some of these tumors were observed.

Monoclonal antibodies against rat mast cells.

Four hybridomas have been isolated which secrete monoclonal antibodies against surface determinants of rat peritoneal mast cells. This could be demonstrated by an indirect immunofluorescence assay. The monoclonal antibodies did also react with a portion of mononuclear phagocytes from the peritoneal cavity but not with other lymphatic cells.

In vitro colonization of thymic primordia by adult bone marrow cells: light scatter profile and separation by flow cytometry.

Adult mouse bone marrow showed a reproducible scatter profile on low angle vs. right angle scatter by flow cytometry and it was possible to sort cells from different regions of the profile. The colonization of the third pharyngeal pouch in vitro was used as a test of thymocyte precursors. Alleles of the Thy-1 surface antigen, as well as the nuclear chromatin pattern of the ichthyosis mutant, were used to monitor chimerism. Thymus-colonizing cells were found in one region of the scatter profile, and these cells were negative for Thy-1 and Ia markers.

Natural immunity to grafts of FLD-3 erythroleukemia cells by irradiated mice.

Mice were irradiated and infused with BALB/c Friend virus-induced FLD-3 erythroleukemia cells. Growth of the cells was estimated by measuring splenic incorporation of 5-iodo-2'-deoxyuridine-125I 5 days after cell transfer. BALB/cJ and C3H mice were 'poor responders' in that FLD-3 cells grew well in their spleens, while mice of other strains were 'good responders', resisting the growth of FLD-3 cells. No H-2 or Fv genetic locus was associated with resistance. Athymic nude mice and mice depleted of marrow tissue by 89Sr or estradiol resisted FLD-3 cells, indicating that the effectors were thymus- and marrow-independent. Silica, carrageenan and Propionibacterium acnes organisms all altered resistance, suggesting a function of macrophages. Neither interferon nor anti-interferon serum treatment altered resistance. Anti-asialo GM1 serum inhibited resistance to FLD-3 cells in vivo and inhibited natural cytotoxic (NC) activity against FLD-3 cells in vitro. NC (FLD-3) activity was greatly decreased in spleens 3 days after irradiation, in contrast with NK (YAC-1) and NC(WEHI-164.1) activities. Moreover, a 3-day delay in infusion of FLD-3 cells 'synergized' with silica in weakening genetic resistance in vivo. Thus, natural immunity to FLD-3 cells in vivo differs from that of genetic resistance to normal bone marrow cell allografts, and the lysis of FLD-3 cells in vitro seems to be mediated by cells which do not easily fit into the definition of natural killer (NK) or natural cytotoxic (NC) cells.