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Inheritance of antibody specificity. II. Anti-(4-hydroxy-5-bromo-3-nitrophenyl) acetyl in the mouse.

Mice of 17 inbred strains produced anti-(4-hydroxy-5-bromo-3-nitrophenyl)-acetyl (NBrP) of three different fine specificity types. Anti-NBrP antibodies of all allotype b mice (five strains tested) had a high relative affinity for (4-hydroxy-3.5-dinitrophenyl) acetyl (NNP) but low for (4-hydroxy-5-cloro-3-nitrophenyl) acetyl (NCP). Another category was characterized by high relative affinity for NCP but low for NNP. This category included most of the tested strains. The third category (CBA and C3H strains) had an intermediate fine specificity. Associated with fine specificity characteristics were anti-NBrP titers, mice of allotype b had lower titers than the other mice. Studies of congenic, recombinant inbred, F1 and backcross mice showed that both fine specificity and the magnitude of the anti-NBrP response of tbalb/C MICE WERE CONTROLLED BY AN ALLOTYPE-LINKED GENE. This gene was dominant over the C57BL/6 ALLELE. Lack of recombinant mice in the backcross generatioterns on the other suggest close linkage between the two genes.

Animals↗

Preovulatory dynamics of ovarian steroid hormones in two mouse strains differing in the rate of meiotic maturation.

Immature females of two inbred strains, KE and CBA, differing in the rate of meiotic maturation, were used in this study. On the 26th day they were treated with 5 IU PMSG (0 h) and 48 h later with 5 IU hCG. Groups of females were killed at 2 h intervals starting with 46 h and ovaries were then dissected for steroid analysis by appropriate RIAs. In both strains hCG injection resulted in a sharp increase in ovarian progesterone content with a simultaneous fall in androgen and oestradiol concentrations. However, in the CBA strain, progesterone concentration started to rise earlier while androgen concentration decreased later than in the KE strain. This subtle difference could be one of the factors contributing to the different maturation rate of KE and CBA strains.

Androgens↗

Spontaneous antiidiotypic antibodies to the NZB Coombs autoantibody.

We have further investigated the phenomenon of spontaneous anti-(Coombs) antiidiotypic antibodies in the F1 hybrids of New Zealand black (NZB) and CBA mice. These mice show an age-related increase in incidence of such antiidiotype during the first year of life. There is no difference between males and females in the occurrence of antiidiotype. Reciprocal hybrids are both affected, so that maternal influence from the NZB strain is not critical. The antiidiotype also occurs in spite of the xid gene. We have so far detected such spontaneous antiidiotype only in (CBA X NZB)F1 hybrids and not in hybrids of NZB with two other strains or in a variety of recombinant inbred strains between NZB and C58. Our results to data suggest extensive shared idiotypy among NZB mice and a limited number of total idiotypes.

Aging↗

Immunogenicity and tolerogenicity of a major house dust mite allergen, Der p I from Dermatophagoides pteronyssinus, in mice and rats.

Primary immunization of different inbred strains of mice with the house dust mite allergen Der p I (from Dermatophagoides pteronyssinus) adsorbed to adjuvant revealed differences in IgE but not IgG responses. Thus, the CBA and C57 Black strains were shown to be high IgE responders in that persistent IgE was induced which lasted for several months. In contrast, the C3H, AKR and Balb/c strains were judged to be poor responders. Subsequent experiments showed that such responses were adjuvant-independent, refractory to irradiation (850 rad) and that they could be adoptively transferred using immune spleen cells in a dose-dependent manner. At sub-optimal doses, adoptively transferred IgE responses were initiated by either intraperitoneal or intranasal challenge of recipients with allergen in the absence of adjuvant. Allergen-specific IgE in rats was also shown to be strain-dependent, with Brown Norway rats, in contrast to Wistar Furth (WF) and Lou/M rats, being the highest responder strain studied. Repeated intranasal administration of soluble allergen induced IgE tolerance in rats but not mice. However, tolerance was restricted to the low IgE responder phenotype strain, WF.

Adjuvants, Immunologic↗

Morphometric analysis of axons myelinated during adult life in the mouse superior cervical ganglion.

In experimental studies addressing the regulation of myelin formation and maintenance by Schwann cells, the sympathetic nervous system of young adult rodents has served a key role as an essentially nonmyelinated yet modifiable control tissue. Nevertheless there is clear evidence of substantial myelination in the superior cervical ganglion (SCG) of normal mice and rats of more advanced age. Against this background, interpretation of experimental outcomes in particular sympathetic tissues will require detailed quantitative control data taking account of animal age. To provide a baseline for future investigations on myelin remodelling, an ultrastructural morphometric study of myelinated fibres in the SCG was undertaken in 4 strains (QS, Balb/C, C57 and CBA) of adult male mice aged 32-72 wk. Numbers of myelinated fibres in SCG cross-sections varied substantially between individual animals, and the mean numbers for QS (132), Balb/C (165) and CBA (254) were significantly higher than that for C57 (32). Both axonal and fibre diameter were distributed unimodally (means for the 4 strains ranged from 2.3-2.4 microns and 3.2-3.6 microns respectively). Myelin spiral length was distributed unimodally and skewed to the right (range of means = 227-357 microns) and was significantly greater in QS mice as compared with the other 3 strains. While the mean g ratio (axonal diameter/fibre diameter) was significantly lower in QS mice than in the other 3 strains, the range for mean g ratio was 0.64-0.73, indicating that myelination had proceeded appropriately even though late in onset in this tissue. The index of circularity was high in all strains, both for axons (range of means = 0.80-0.88) and fibres (range of means = 0.84-0.89). The small axonal and fibre diameter and unimodal distribution are consistent with the characteristics of autonomic myelinated fibres and it is probable that most are postganglionic sympathetic fibres arising within the SCG. In terms of providing a sufficient population of myelinated fibres for future experimental studies, the QS, Balb/C and CBA strains would be preferable to C57 mice.

Animals↗

Various epithelial and non-epithelial tumors spontaneously occurring in long-lived mice of A/St, CBA, C57BL/6 and their hybrid mice.

Various kinds of epithelial and non-epithelial tumors, and tumor-like lesions spontaneously developed in long-lived mice of strains A/St, C57BL/6 and CBA, and of (C57BL/6 X CBA) F1 hybrids, all of which had been fed in the 2nd Department of Pathology, Gifu University School of Medicine. Some tumors were successfully transplanted into the same strain of mice. An interesting tumor line showing phagocytic activity and growing only in the liver even when inoculated subcutaneously, which was obtained from a reticulum cell neoplasm, Type A by Dunn, originated in the liver of a (C57BL/6 X CBA) F1 hybrid male mouse.

Aging↗

Stereoselective enhancement of nociception by opioids in different strains of mice.

The effects of Mr2096, Mr2097, diprenorphine, (-)bremazocine and Mr2266 on jumping latencies were evaluated in Swiss, CXBK, C57BL, CXBH and CBA strains of mice. Mr2096 and Mr2097 respectively produced analgesia and hyperalgesia in these strains of mice. Thus their effects on nociception were mediated by stereoselective opioid receptors. Diprenorphine also produced hyperalgesia which might be mediated by both mu and kappa receptors. Kappa receptors also appeared to mediate hyperalgesia at least in Swiss and CBA strains, as both (-)bremazocine and Mr2266 shortened the jumping latencies.

Animals↗

[Morphological study of the damaging effect of an EB vaccine strain of the plague microbe in inbred mice].

The data obtained during the study of the morphological changes in the internal organs and blood of 6 mouse strains at the early stages of anti-plague immunity are presented. It has been established that the introduction of 5.10(3) and 1.10(5) m. b. of the EV vaccine strain resulted in the development of morphological changes typical of residual virulence. The degree of these changes depended on the haplotype of the animals and the dose used. The most resistant to injury induced by EV strain were CBA mice (haplotype H-2k) and the most sensitive were C57BL/6 mice (haplotype H-2b).

Adrenal Glands↗

Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice.

We produced transgenic mice which overexpress human IL-6 in pancreatic beta cells of C57BL/6 x CBA and non-obese diabetic (NOD) mice. Transgenic C57BL/6 x CBA mice back-crossed onto a C57BL/6 background do not develop insulitis or diabetes. In contrast, NOD/F1 transgenic mice develop a lymphocytic infiltrate of pancreatic islets which is not seen in negative littermates. Immunohistochemistry reveals these cells to be predominantly CD4+, CD8+, B220+ cells. Despite the insulitis, these mice do not develop diabetes. Transgenic rat insulin promoter-IL-6 mice were therefore also made on an inbred NOD background. These mice showed no difference in the onset or extent of insulitis when compared with non-transgenic NOD mice and no difference was found in the phenotype of the infiltrating cells. However, transgenic NOD mice had lower average fasting glucose levels and delayed onset of diabetes compared with age and sex matched littermate negative NOD mice. As a consequence, transgenic NOD mice also had longer survival than littermate negative NOD mice. We conclude that the expression of IL-6 by beta cells does not cause insulitis or diabetes in C57BL/6 x CBA mice, but that the interaction of IL-6 and diabetes susceptibility genes causes insulitis in NOD/F1 mice. Since IL-6 delays the onset of diabetes and prolongs survival of NOD mice, it is possible that the protective effect is caused by local IL-6 action on the islets, by the infiltrating lymphocytes or both.

Animals↗

Variable susceptibility to immune complex glomerulonephritis among mice sharing the same major histocompatibility complex.

Three inbred strains of mice were identified which demonstrated different susceptibilities to induction of immune complex glomerulonephritis (ICGN) despite sharing the same major histocompatibility complex haplotype (H-2k). Groups of mice from each of these three strains, B10.BR, CBA and C3H/HeJ, were injected with one of two different dose schedules of horse apoferritin (HAF) for 4 weeks, after which glomerular morphology, immunoglobulin deposition, and serum anti-HAF antibody levels were examined. With either dose schedule, only those mice which demonstrated a high level antibody response developed ICGN and glomerular immunoglobulin deposition. These results suggest that susceptibility to ICGN in this model is related to the level of antigen exposure and to the magnitude of the antibody response, which is not under strict control of the major histocompatibility complex.

Animals↗

[Mechanical properties of the intercellular contacts of hepatocytes of inbred strains of mice and mice predisposed to spontaneous hepatomas].

The adhesiveness of hepatocytes was evaluated in 7 inbred mice and compared to the reported data on the incidence of spontaneous hepatomas. The adhesiveness was shown to be significantly less in mice predisposed to spontaneous hepatomas as compared to more resistant species. Electron microscopy revealed the presence of little and highly adhesive areas (HAA) in nonspecialized regions of hepatocytic contacts, this presence being shown by elevated (20-30 mm Hg) hydrostatic pressure in the liver blood bed. The amount and mechanical strength of HAA was less in CBA mice predisposed to spontaneous hepatomas as compared to resistant C57B1 mice, and correlated with cell adhesiveness.

Age Factors↗

Antibody response in C3H mice injected with CBA lymphoid cells as detected by membrane immunofluorescent staining.

Lymphocytes from CBA mice are strongly responsive to cells from the H-2-identical strain C3H in vitro (MLC), whereas C3H lymphocytes are poorly reactive against CBA cells. Immunization of CBA mice with C3H lymphocytes did not yield any detectable specific antibodies. On the other hand, C3H mice immunized with CBA cells produced specific antibodies as detected by membrane immunofluorescence. Mice of the strains AKR and DBA/2 also possess this specific membrane alloantigen. We thus conclude that it is now possible to discriminate among lymphocytes of CBA and C3H origin.

Animals↗

[Primary and secondary immune response of mice to polysaccharide antigens of meningococcal serogroups A and C].

The peculiarities of the primary immune response, the formation of immunological memory and the secondary immune response to serogroup A and C meningococcal polysaccharides were studied in 7 strains of inbred mice, hybrids F1 and in noninbred animals. The passive local hemolysis test and the passive hemagglutination test indicated that the intensity of immune response to A and C polysacchardies depended on the genotype of the animals: both antigens induced the most intense response in CBA and BALB/c mice. The primary immune response to the both antigens was characterized by a short latent period, a rapid (by days 4-5) increase in the amount of antibody-producing cells in the spleen and in antibody titer in the blood serum to the maximum level, and a pronounced decrease inantibody formation by days 6-7 followed by a gradual extinction of the response. A single injection of A and C polysaccharides in a dose of 0.5 microgram induced the formation of immunological memory in mice, persisting for at least 4 weeks and manifesting after reimmunization as the increased or more prolonged synthesis of IgM and IgG.

Animals↗

Genotypic and phenotypic characterization of six new recombinant congenic strains derived from NOD/Shi and CBA/J genomes.

Recombinant Congenic Strains (RCS) are useful for dissecting complex polygenic traits. Here, we describe genetic and phenotypic characterization of six new RCS generated from outcrosses between NOD/Shi and CBA/LsLt, followed by sib mating of first backcross progeny (to CBA) for 20 generations, whereupon genetic and phenotypic analysis commenced. Four of the RCS were selected on the basis of residual heterozygosity present at F20 in one of the three original RCS. Contrary to expectations for RCS developed at first backcross, all derived at least 50% of the polymorphic markers typed from the NOD parental strain. Development of autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD is a strain-specific characteristic. The major genetic component predisposing NOD mice to IDDM, their H2(g7) haplotype, was present in all RCS. Nevertheless, the presence of variable amounts of CBA genome at non-MHC loci conferred complete resistance in all RCS to spontaneous IDDM development, and rendered them strongly resistant to cyclophosphamide-induced IDDM. Although the RCS more resemble NOD in regard to certain strain-specific characteristics, such as prolificacy, an immunologic phenotype that was significantly reduced when compared to both parental strains was the number of peripheral CD8(+) T cells. Given the genetic characterization presented, these new RCS should prove valuable to investigators interested in studying genes controlling differential susceptibilities distinguishing the NOD and CBA inbred strain backgrounds.

Animals↗

Differential maintenance and frequency-dependent tuning of LTP at hippocampal synapses of specific strains of inbred mice.

Transgenic and knockout mice are used extensively to elucidate the molecular mechanisms of hippocampal synaptic plasticity. However, genetic and phenotypic variations between inbred mouse strains that are used to construct genetic models may confound the interpretation of cellular neurophysiological data derived from these models. Using in vitro slice stimulation and recording methods, we compared the membrane biophysical, cellular electrophysiological, and synaptoplastic properties of hippocampal CA1 neurons in four specific strains of inbred mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms/J. Hippocampal long-term potentiation (LTP) induced by theta-pattern stimulation, and by repeated multi-burst 100-Hz stimulation at various interburst intervals, was better maintained in area CA1 of slices from BL/6J mice than in slices from CBA and DBA mice. At an interburst interval of 20 s, maintenance of LTP was impaired in CBA and DBA slices, as compared with BL/6J slices. When the interburst interval was reduced to 3 s, induction of LTP was significantly enhanced in129/SvEms slices, but not in DBA and CBA slices. Long-term depression (LTD) was not significantly different between slices from these four strains. For the four strains examined, CA1 pyramidal neurons showed no significant differences in spike-frequency accommodation, membrane input resistance, and number of spikes elicited by current injection. Synaptically-evoked glutamatergic postsynaptic currents did not significantly differ among CA1 pyramidal neurons in these four strains. Since the observed LTP deficits resembled those previously seen in transgenic mice with reduced hippocampal cAMP-dependent protein kinase (PKA) activity, we searched for possible strain-dependent differences in cAMP-dependent synaptic facilitation induced by forskolin (an activator of adenylate cyclase) and IBMX (a phosphodiesterase inhibitor). We found that forskolin/IBMX-induced synaptic facilitation was deficient in area CA1 of DBA/2J and CBA/J slices, but not in BL/6J and 129/SvEms/J slices. These defects in cAMP-induced synaptic facilitation may underlie the deficits in memory, observed in CBA/J and DBA/2J mice, that have been previously reported. We conclude that hippocampal LTP is influenced by genetic background and by the temporal characteristics of the stimulation protocol. The plasticity of hippocampal synapses in some inbred mouse strains may be "tuned" to particular temporal patterns of synaptic activity. From a broader perspective, our data support the notion that strain-dependent variation in genetic background is an important factor that can influence the synaptoplastic phenotypes observed in studies that use genetically modified mice to explore the molecular bases of synaptic plasticity.

Action Potentials↗