Calretinin and calbindin distribution patterns specify subpopulations of type I and type II spiral ganglion neurons in postnatal murine cochlea.

As the first neural element in the auditory pathway, neurons in the spiral ganglion shape the initial coding of sound stimuli for subsequent processing. Within the ganglion, type I and type II neurons form divergent and convergent innervation patterns, respectively, with their hair cell sensory receptors, indicating that very different information is gathered and conveyed. Layered onto these basic innervation patterns are structural and electrophysiological features that provide additional levels of processing multifaceted sound stimuli. To understand the nature of this additional complexity of signal coding, we characterized the distribution of calretinin and calbindin, two regulators of intracellular calcium that serve as markers for neuronal subpopulations. We showed in acute preparations and in vitro that calretinin and calbindin staining levels were heterogeneous. Immunocytochemical analysis of colocalization further showed that high levels of staining for the two molecules rarely overlapped. Although varied amounts of calbindin and calretinin were found within each tonotopic location and neuronal type, some distinct subdistributions were noted. For example, calretinin levels were highest in neurons innervating the midcochlea region, whereas calbindin levels were similar across the entire ganglion. Furthermore, we noted that apical type II neurons, identified by antiperipherin labeling, had significantly lower levels of calretinin and higher levels of calbindin. We also established that the endogenous firing feature of onset tau of the subthreshold response showed a pattern related to quantified calretinin and calbindin staining levels. Taken together, our results suggest an additional dimension of complexity within the spiral ganglion beyond that currently categorized.

To drive or be driven: the path of a mouse model of recurrent pregnancy loss.

This review is an example of the use of an animal model to try to understand the immune biology of pregnancy. A well-known model of recurrent spontaneous pregnancy loss is put in clinical, historical, and theoretical context, with emphasis on T cell biology.

Gravity receptor aging in the CBA/CaJ strain: a comparison to auditory aging.

The CBA/CaJ mouse strain is commonly used as a control as it has no known genetic mutations affecting the inner ear, maintains hearing sensitivity throughout life, and serves as a background for creating new genetic strains. The purpose of the present study was to characterize the effects of age and gender on gravity receptor function and compare functional changes between auditory and vestibular modalities. Vestibular-evoked potentials (VsEPs), auditory brainstem responses (ABRs), and distortion product otoacoustic emissions were measured in 131 mice. VsEP thresholds deteriorated an average of 0.39 dB re: 1.0 g/ms per month and at the oldest ages (18-23 months old) showed an average loss of 49% of VsEP dynamic range. No significant gender differences were found for VsEPs. ABR thresholds increased by an average of 1.35, 1.38, and 1.15 dB pe SPL per month for ABR stimulus frequencies of 8, 16, and 32 kHz, respectively, demonstrating an average decrease in auditory dynamic range of 25-35% at advanced ages. Both modalities declined with age. Age-related decreases in gravity receptor sensitivity should be considered when using the CBA/CaJ strain for vestibular studies.

Individual and typological behavioral characteristics of CBA/CaLac mice.

Individual characteristics of higher nervous activity were studied in CBA/CaLac mice. The animals were divided into groups by the parameters of drinking response conditioning in a complex spatial environment. As distinct from bad learners, good learners exhibited higher orientation and exploratory activity in the open field, rapid adaptation, and low ability to retain the responses. Changes in conditioned reflex activity during neuroses were more pronounced in good learners.

Circadian variation of mouse aqueous humor protein.

PURPOSE: The first aim was to document the 24 h pattern of total protein concentration in aqueous humor of the C57BL/6J mouse strain under various environmental light-dark conditions. The second aim was to determine the diurnal/nocturnal change of aqueous humor protein concentration in the CBA/CaJ mouse strain reported to show a unique absence of diurnal/nocturnal elevation of intraocular pressure (IOP). METHODS: Mice of both strains were entrained to a daily 12 h diurnal/light (6 AM to 6 PM) and 12 h nocturnal/dark cycle. Total protein concentrations of aqueous humor were determined using specimens collected from C57BL/6J mice every 4 h under standard light-dark, acute constant dark, and acute constant light conditions. Aqueous humor protein concentrations in CBA/CaJ mice were determined at three diurnal times and three nocturnal times. RESULTS: The C57BL/6J mouse strain showed a higher aqueous humor protein concentration during the diurnal period than during the nocturnal period under standard light-dark conditions. This pattern persisted under acute constant dark and was modulated under acute constant light. The CBA/CaJ mouse strain showed a similar diurnal/nocturnal decrease of total aqueous humor protein concentration. CONCLUSIONS: Endogenous circadian variation of aqueous humor protein concentration occurs in the C57BL/6J mouse strain. The nocturnal concentration is significantly lower than the diurnal concentration. A similar diurnal/nocturnal decrease of aqueous humor protein concentration occurs in the CBA/CaJ mouse strain, indicating that this change of aqueous humor protein is unrelated to the diurnal/nocturnal pattern of IOP.

[Induction of meiotic disturbances in spermatocytes I by pheromones as an inhibiting mechanism of male reproductive function in house mice].

The influence of pheromons on reproduction and other important physiological characteristics has been reported for many mammalian species. However, mechanisms of this action at the level of target cells still remain unclear. A study was made of the influence of non-identified pheromones from adult males and a female pheromone 2,5-dimethylpyrazine on germ cells of CBA inbred strain mice. Cytogenetic analysis shows a significant increase in such meiotic disturbances as multivalent associations and autsomal univalents 24 h after exposure to pheromonal cues. Results of in situ hybridization show that the level of c-fos and c-jun expression is significantly higher 3.5 h after exposure to pheromones of adult males. It is likely that destabilization of chromosomal apparatus in dividing meiotic cells forms the basis of some reproductive effects of murine pheromones. Possible mechanisms of pheromone influence on reproduction are discussed.

Interstrain variation in murine aerobic capacity.

PURPOSE: The contribution of genetic factors to aerobic capacity is unknown. The purpose of this study was to measure maximal aerobic performance among inbred strains of mice to provide basic heritability estimates. METHODS: Eight female mice, 8 to 10 wk old, in 10 inbred strains (A/J, AKR/J, Balb/cJ, C(3)H/HeJ, C57Bl/6J, C57L/J, C(3)Heb/FeJ, CBA/J, DBA/2J, and SWR/J) were run on a treadmill until exhaustion. The protocol started at 22 m.min(-1) and increased in speed approximately 6 m.min(-1) every 4 min. After 4 min at 42.4 m.min(-1), the grade was increased 2% every 4 min thereafter until the mouse could not run off of the shock grid (150 V; 1.5 mA). RESULTS: There were significant differences between inbred strains in maximal duration of exercise accomplished (P < 0.0001). The order of strain-specific exercise duration was Balb/cJ > SWR/J > CBA/J > C57L/J > C3H/HeJ > C3Heb/FeJ > C57Bl/6J > AKR/J > DBA/2J > A/J. Two measures of heritability in the broad sense, intraclass correlation (0.73), and the coefficient of genetic determination (0.58) were both significant. CONCLUSION: These data indicate that there is a strong genetic contribution to aerobic capacity in mice.

Vulnerability to noise-induced hearing loss in 'middle-aged' and young adult mice: a dose-response approach in CBA, C57BL, and BALB inbred strains.

Vulnerability of the cochlea to noise-induced permanent threshold shifts (NIPTS) was examined in young adult (1-2 months) and 'middle-aged' (5-7 months) CBA/CaJ, C57BL/6J, and BALB/cJ inbred mice. For each age and strain, a dose-response paradigm was applied, whereby groups of up to 12 animals were exposed to intense broadband noise (110 dB SPL) for varying durations. Exposure durations reliably associated with <10% and >90% probability of a criterion amount of NIPTS (determined 2 weeks post-exposure) were identified, and the minimum NIPTS exposure and the slope of the dose-response relation were then derived by numerical modeling. For all three strains, young adult mice were more susceptible to NIPTS than older adults; That is, a shorter exposure was able to cause NIPTS in the younger mice. Strain comparisons revealed that C57 mice were more susceptible than CBAs in the older age group only. At both ages examined, however, BALB mice were most susceptible to NIPTS. When animals with a similar amount of NIPTS were compared, outer hair cell loss in the cochlear base was more widespread in the younger animals. BALB mice appear particularly susceptible to noise-induced outer hair cell loss throughout life. Our data suggest that the mechanism or site of noise injury differs between young adults and older adults, and may depend on genetic background. The finding that both BALB and C57 mice, which show pronounced age-related hearing loss, are also especially vulnerable to noise supports the notion that genes associated with age-related hearing loss often act by rendering the cochlea susceptible to insults.

High resolution magnetic resonance angiography non-invasively reveals mouse strain differences in the cerebrovascular anatomy in vivo.

High resolution magnetic resonance angiography (MRA) revealed highly variable arterial cerebrovascular structures in mice from different strains and within the same strain. C57Black/6 mice presented small unilateral anastomoses between the posterior cerebral and the superior cerebellar arteries. Well developed, either unilateral or bilateral, posterior communicating arteries (PcomA) were detected on CBA mice. The arterial structure of CD1 mice ranged from no detectable anastomoses to well developed, unilateral PcomAs. SV-129 mice showed significantly shorter middle cerebral arteries compared to the other strains, and clear bilateral anastomoses between the posterior cerebral and the superior cerebellar arteries. Because of its non-invasiveness, MRA may be of importance in murine stroke studies by enabling the selection of animals and/or the side for performing the surgical intervention, and the verification of its success. Magn Reson Med 44:252-258, 2000.

[The determination of the parameters of anxiety in C57BL/6J, CBA/Lac and BALB/c mice under the influence of a serotonin C1A receptor agonist [correction of antagonist]. / Vyiavlenie parametrov trevozhnosti u myshei linii C57BL/6J, CBA/Lac i BALB/c pod vliianiem agonista serotoninovykh retseptorov C1A.

Three strains of inbred mice, C57BL/6J (C57), CBA/Lac (CBA), and BALB/c (BALB) were examined in the elevated plus-maze after the injection of an anxiotropic drug, a 5-HT1A agonist ipsapirone (3 mg/kg; i.p.; 30 min). Treatment with ipsapirone had different anxiogenic effects on the behavior of mice in accordance with their genotype. In C57 mice the drug produced a significant decrease in the percentage of the open-arm time and the number of open-arm entries as well as in the number of full entries (when an animal was between the half and the end of an open-arm) and in the number of head dippings. Besides; the number of C57 mice which performed full entries after the ipsapirone injection decreased. In CBA mice ipsapirone reduced the number of enclosed-arm entries, the number of the passages from one enclosed arm to another and the number of head dippings. Only the number of passages dropped in BALB mice after the drug injection. Probably, just these parameters reflect anxiety in mice of the genotypes under study. It was suggested that the sensitivity of 5-HT1A receptors in C57 mice is the highest.

Effects of exposure to an augmented acoustic environment on auditory function in mice: roles of hearing loss and age during treatment.

The effects of exposure to an augmented acoustic environment (AAE) on auditory function were evaluated in mouse strains that exhibit various degrees and time courses of progressive hearing loss (BXD-22, BXD-12, BXD-16, BXD-14, BALB/cJ), and in normal-hearing CBA/CaJ mice. Beginning at age 25 days, mice were exposed 12 h every night to a 70 dB SPL broadband noise AAE. The AAE was maintained for at least 30 days in each strain. Same-strain control mice were age-matched and maintained under normal vivarium acoustic conditions. The auditory brainstem response (ABR), acoustic startle response amplitude, and prepulse inhibition (PPI) were used to assess the auditory system. Exposure to the AAE resulted in improved auditory performance (better PPI, lower ABR thresholds) when hearing impairment was present, but not when hearing was normal. The ameliorative effects occurred irrespective of a mouse's age at the onset of hearing loss, as long as initiation of AAE treatment preceded the occurrence of severe hearing loss. If AAE treatment was delayed beyond such a point, loss of threshold sensitivity progressed as usual, although PPI could still benefit. Finally, AAE treatment can slow, but not prevent, the occurrence of severe genetically determined hearing loss.

[The characteristics of the manifestation of hereditarily induced anxiety in male C57Bl/6J and CBA/Lac mice]. / Osobennosti proiavleniia nasledstvenno-obuslovlennoi trevozhnosti u samtsov myshei linii C57Bl/6J i CBA/Lac.

Behavior of male mice of C57Bl/6J and CBA/Lac strains was tested in the elevated plus-maze and open field in order to estimate state anxiety in novel conditions. The cube and partition tests were used to reveal trait anxiety in the familiar conditions of the home cage. It is concluded that genetically defined state anxiety is more pronounced in CBA/Lac mice and trait anxiety in C57Bl/6J strain.

The response of transgenic mice to beta-adrenergic agonist administration is different from that of normal mice.

Eighteen transgenic mice carrying an ovine metallothionein la-ovine growth hormone (oMTla-oGH) transgene and 18 littermate normal mice were used to investigate the effects of transgene expression and clenbuterol administration on growth performance and skeletal muscle characteristics. The oGH transgene was activated from 21 d of age, and half of the mice were fed 15 ppm clenbuterol from 42 to 70 d of age. All mice were killed at 70 d of age after 4 wk of treatment, and organs and muscles were dissected, weighted, and analyzed. Transgenic mice (TM) gained 2.6 times more than normal mice (NM). However, TM had a significantly lower (-20%, P < .01) proportion of muscle, expressed as percentages of body weights, and a higher percentage of heart (+10%), liver (+26%, P < .01) and spleen (+64%, P < .01) than NM. Clenbuterol improved the weight gain of TM by 20%, compared with 10% for NM. The growth-promoting effect of clenbuterol was almost exclusively confined to skeletal muscle (24% increase) in NM, in contrast to a more generalized growth increase in all tissues including skeletal muscle (11% increase) in TM. The skeletal muscles of TM were longer but smaller in diameter due to 30% smaller muscle fiber cross-sectional area. Clenbuterol increased the muscle fiber size of all fiber types by 60% in NM, compared to 30% in TM. Muscle DNA concentrations and content were higher (P < .05) in TM than in NM, and clenbuterol administration decreased DNA concentrations but not total DNA content for both genotypes. Cathepsin B, C, and H activities were higher (P < .01) in TM muscle, but the significance is not clear at the present time, although it points to a potential for greater protein degradation and(or) turnover rates as suggested by smaller muscle weights.

[Interstrain differences in extrapolation capacity and exploration of a cruciform maze correlate with various indices of monoamine metabolism in the brain]. / Mezhlineinye razlichia v sposobnosti k ékstrapoliatsii i v osvoenii krestoobraznogo labirinta korreliruiut s raznymi pokazateliami obmena monoaminov mozga.

C57BL/6J (B6) and CBA mice with normal karyotype and respective substrains carrying robertsonian translocation (fusion) of chromosomes 8 and 17 (Rb) were compared in their ability to extrapolate the direction of stimulus movement disappearing from the field of vision, rearings and hole-poke responses, and exploration strategies in a plus-maze. Rb mice were shown to be superior to normal karyotype groups in extrapolation behaviour. The pattern of interstrain differences in noradrenaline level in the cortex and serotonin turnover indices in the hippocampus correlated with differences in extrapolation ability, while exploration strategies in the plus-maze correlated with differences in dopamine level and its turnover rate in the neocortex and striatum. The data demonstrated that chromosomal rearrangement inducing behavioural differences was accompanied also by discrete neurochemical changes, and that spatial exploration strategies (being probably the constituent of general spatial abilities of mice) were to a large extent independent from extrapolation ability which was regarded as the index of animal reasoning capacity.

Sensorineural hearing loss alters recovery from short-term adaptation in the C57BL/6 mouse.

Several strains of laboratory mouse (Mus musculus) have a pattern of hearing loss which resembles that found in humans. The C57BL/6 strain of mouse has a genetic defect that results in degeneration of the organ of Corti, originating in the basal, high-frequency region and then proceeding apically over time. The end result is a severe-to-profound sensorineural hearing loss (SNHL) by 14 months of age. In contrast, auditory function of the CBA strain remains normal through its early life span then slowly declines later in life, much like that typified by human presbycusis. The purpose of the present study was to compare ABR (peak 5) forward masking recovery functions in young, normal-hearing CBA and C57BL/6 mice to hearing-impaired C57BL/6 mice. ABR audiograms were obtained prior to collecting the tone-on-tone forward masking data. Masking was defined as a 50% reduction in the P5 component of the ABR, elicited and masked by 12 kHz tone bursts, using masker/probe time delays from 0 to 100 ms. Time constants were computed from an exponential model fit to the recovery functions (masker level vs. time delay). In hearing-impaired animals there was a significant increase in recovery from short-term adaptation as measured by the time constants, as well as a significant latency shift in the P5 component. The effects of SNHL on the recovery of the P5 component from short-term adaptation was comparable to that reported behaviorally for human hearing-impaired listeners and physiologically from the inferior colliculus (IC) of chinchillas suffering permanent threshold shifts.

Is spontaneous resorption in the DBA/2-mated CBA/J mouse due to a defect in "seed" or in "soil"?

PROBLEM: Recurrent spontaneous resorption in DBA/2-mated CBA/J mice has been attributed to damage by NK-lineage cells and TNF-alpha beginning several days after implantation. However, some recent data have suggested CBA/J female mice have a high proportion of preimplantation embryo abnormalities resulting in defective in vitro implantation and impaired trophoblast outgrowth. Could spontaneous abortion be due to a defective embryo ("seed") rather than a hostile post-implantation uterine lining ("soil"). METHOD: Mated CBA/J females were manipulated so as to have high spontaneous abortion rates and a high percent abnormal embryos, or low resorption rates and a low percent abnormal embryos. Embryos from low aborting females were transferred into high aborting female recipients that were pseudopregnant, and vice versa. RESULTS: Abnormal embryos from females with high abortion rates implanted in low aborting females and did not show any greater tendency to resorb than normally developed embryos in these recipients. By contrast, normal embryos to some extent and abnormal embryos to a much greater extent, gave a high abortion rate when the recipient female was a high aborter. CONCLUSION: Properties of the "soil" into which embryos implant determines the likelihood of success or failure (abortion). Abnormal pre-implantation embryos can be "rescued" by "good soil"; "sick soil" damages both normal and abnormal embryos. Defining the cellular and molecular mechanisms may be useful in understanding basic mechanisms leading to aborting and nonaborting pregnancy.

Carcinogenic effects of cytostatic protocols in CBA/Ca mice.

An in vivo mouse model was developed in order to study the characteristics of secondary tumor induction by cytostatic drug combinations used in human anticancer treatment. In this model we have proved the carcino-leukemogenic effects of widely used chemotherapeutical drug combinations (CHOP, COPP, COPBLAM, VAM). The carcinogenic hazards of cyclophosphamide and other alkylating drugs could also be demonstrated in our model.

[The effect of the prolonged experience of aggression and subordination on the adrenal cortical and androgenic functions of inbred male mice]. / Vliianie dlitel'nogo opyta agressii i podchineniia na adrenokortikal'nuiu i androgennuiu funktsii samtsov inbrednykh myshei.

Repeated experience of aggression and submission in daily agonistic confrontations differently changed stress response in winners and losers of CBA/Lac and C57BL/6J strains. Experience of defeats was accompanied by expressed decrease of testosterone level in losers. Number of hemorrhages and erosions was significantly more in losers when compared to winners. Some strain differences in stress reaction were found in winners and losers as compared to controls.

Variation among inbred and linecross mice in response to fescue toxicosis.

Variation in response to fescue toxicosis was examined in inbred and linecross mice. In Exp. 1, exposure to a 50% endophyte-infected tall fescue diet (E+) reduced ADG of males from six inbred lines, but ADG of males from one line was modestly higher on E+. Lines differed (P < .01) for reproductive organ weight, but the diet x line interaction was not significant. In Exp. 2, an apparently susceptible (C57) and an apparently resistant line (FVB) were mated to produce inbred and linecross offspring. The reduction in weight gain caused by the E+ diet did not differ significantly among the genetic groups. In Exp. 3, C57 and C57 backcrosses had smaller reductions in ADG during E+ vs control feeding periods than FVB and FVB backcrosses (P < .10). In Exp. 4, the E+ diet reduced litter size of mates of C57 males by one pup, whereas litter size of mates of FVB males was four pups larger (interaction P = .07). Neither diet, line, nor their interaction affected male reproductive organ weights or tissue proportions in testis cross-sections. In Exp. 5, the E+ diet did not affect weight gain of C57 or FVB males, but effects of the E+ diet on litter size of mates were similar to those in Exp. 4. Percentage of abnormal sperm was increased in C57 males on the E+ diet but decreased in FVB males (Exp. 5). Differences among inbred lines in susceptibility to fescue toxicosis may depend on severity of the challenge and life cycle stage when the challenge is imposed.

[The role of the sex hormones in regulating the spermatogenesis process in different strains of mice irradiated at low doses of gamma quanta]. / Rol' polovykh gormonov v reguliatsii protsessa spermatogeneza u myshei raznykh linii, obluchennykh v malykh dozakh gamma-kvantami.

Intact BALB/c and CBA mice distinct in the total number of germ cells and testosterone level in blood plasma were exposed to doses of 0.1 and 0.25 Gy. Being tested 4-8 days after irradiation the BALB/c mice display compensatory-protective reaction which promote the maintenance of the germ cell number by active division of all spermatogonia types including the reserve ones. The CBA mice use the reserve later and only when the cells have reduced their proliferation activity or died. Testosterone plays a significant role in the process as the increase in its concentration stimulates proliferation activity and promotes mitosis block.