The faded mouse is a coat color mutant that shows faded coat color and age-related loss of pigmentation. This mutation is transmitted by an autosomal recessive gene with 100% penetrance. In the present study, we carried out linkage analysis of the faded (fe) gene using intra-specific backcross panels. Affected faded mice were carefully confirmed by their faded coat color at about 4 weeks of age. In the intra-specific backcross between faded and CBA mice (n=198), the fe gene was mapped to a region 2.1 cM distal to D10mit191. Therefore, the gene order was defined as follows: centromere-D10mit51 (12.4+/-2.4 cM)-D10mit191 (2.1+/-1.0 cM)-fe-D10mit44 (13.3+/-2.4 cM)-D10mit42 (14.4+/-2.5 cM). This linkage map of the fe locus will provide a good entry point to isolate the fe gene. Since the faded mouse has pigmentary abnormalities, this mutant may be a useful model for studies of pigmentary abnormalities in humans.
Animals ; Chromosomes, Human, Pair 10 ; Gene Order ; Genes, Recessive ; Humans ; Mice ; Mice, Inbred CBA ; Penetrance ; Pigmentation

Due to the advantages in genetic manipulation, mice have become one of the most commonly used mammalian models for the study of mechanisms underlying myopia development. However, the vast majority of laboratory mouse strains are incapable of synthesizing melatonin, a neurohormone that may play an important role in myopia generation in humans. The present study investigated refractive development profiles in the CBA/CaJ mouse, a strain proficient in melatonin, and determined whether and how its refractive development could be affected by form-deprivation. Eccentric infrared photoretinoscopy revealed that this animal could be stably refracted, and the refractive error underwent developmental changes, which increased with age in the hyperopic direction and eventually got stable approximately 9 weeks after birth. The absolute values of refractive error in CBA/CaJ mice were larger than those of age-matched C57BL/6 mice, whereas the time points when refractive error reached steady state were similar between the two strains. Five weeks of form-deprivation applied to 3-week-old CBA/CaJ mice by translucent occluder wear caused a significant myopic shift in refractive error, indicating that this strain could be adequately used as a myopia model.
Animals ; Disease Models, Animal ; Eye ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Refraction, Ocular ; Sensory Deprivation

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

In this study, cytometric beads array(CBA) was used to determine the immunoglobulin content in humoral immunity evaluation of biomedical materials. The bovine-derived acellular dermal matrix was selected as a test sample and implanted into Balb/C mice subcutaneously to 4 weeks according to the high, medium and low dose groups. Four weeks later, IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM were measured by CBA. The data of the test group and the control group were analyzed statistically. The results showed that compared with the negative control group, there was no significant difference in the IgG3, IgA content in the positive control group, while the IgG1, IgG2a, IgG2b, and IgM contents were significantly higher than the negative control group; no significant differences were seen in the sample groups. The results show that the method is suitable for analysis of immunoglobulin content in humoral immunity evaluation of biomedical materials.
Animals ; Cattle ; Immunity, Humoral ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA

PURPOSE: Lung transplantation is now accepted as an effective therapy for end-stage pulmonary vascular and parenchymal diseases. Rejection is a major impediment to long-term survival of lung transplant recipients. Lung allograft rejection has been studied in various animal models. To study the immunological mechanism of its rejection the studies on lung allograft rejection must be performed in inbred animals such as mice or rats. However, it is very delicate and difficult to transplant the lung in small inbred animals, especially in mice. The technical difficulty hampered the investigations of lung allograft rejection. METHODS: This study introduced the new lung transplantation technique in mice for immunological study, subcutaneous lung tissue transplantation, in which the piece of lung tissue with 1-1.5 mm thickness was introduced subcutaneously through incision site on flank and transplanted to subcutaneous site of shoulder of mouse. Histological changes were followed up in transplanted lung tissues for 18 to 21 days. Lung tissues from CBA mice or Balb/c mice were subcutaneously transplanted to Balb/c mice in experimental or control group respectively. RESULTS: Histological changes in the grafts of experimental groups could be divided into 4 phases, inflammatory, immunological, necrotic and fibrotic phase. Immunological or necrotic phase in this study correlated with grade 1-3 or grade 3-4 of acute lung rejection classified by the Lung Rejection Study Group. CONCLUSION: It is concluded that the subcutaneous lung tissue transplantation can be a technique for immunological study on acute lung allograft rejection in mice.
Allografts ; Animals ; Lung Transplantation* ; Lung* ; Mice ; Mice, Inbred CBA ; Models, Animal ; Rats ; Shoulder ; Tissue Transplantation ; Transplantation ; Transplants

BACKGROUNDPrevious studies have suggested that primary degeneration of hair cells causes secondary degeneration of spiral ganglion neurons (SGNs), but the effect of SGN degeneration on hair cells has not been studied. In the adult mouse inner ear ouabain can selectively and permanently induce the degeneration of type 1 SGNs while leaving type 2 SGNs, efferent fibers, and sensory hair cells relatively intact. This study aimed to investigate the dynamic changes in hair cell ribbon synapse induced by loss of SGNs using ouabain application to the round window niche of adult mice.

METHODSIn the analysis, 24 CBA/CAJ mice aged 8-10 weeks, were used, of which 6 normal mice were used as the control group. After ouabain application in the round window niche 6 times in an hour, ABR threshold shifts at least 30 dB in the three experimental groups which had six mice for 1-week group, six for 1-month group, and six for 3-month group. All 24 animals underwent function test at 1 week and then immunostaining at 1 week, 1 month, and 3 months.

RESULTSThe loss of neurons was followed by degeneration of postsynaptic specializations at the afferent synapse with hair cells. One week after ouabain treatment, the nerve endings of type 1 SGNs and postsynaptic densities, as measured by Na/K ATPase and PSD-95, were affected but not entirely missing, but their partial loss had consequences for synaptic ribbons that form the presynaptic specialization at the synapse between hair cells and primary afferent neurons. Ribbon numbers in inner hair cells decreased (some of them broken and the ribbon number much decreased), and the arrangement of the synaptic ribbons had undergone a dynamic reorganization: ribbons with or without associated postsynaptic densities moved from their normal location in the basal membrane of the cell to a more apical location and the neural endings alone were also found at more apical locations without associated ribbons. After 1 month, when the neural postsynaptic densities had completed their degeneration, most ribbons were lost and the remaining ribbons had no contact with postsynaptic densities; after 3 months, the ribbon synapses were gone except for an occasional remnant of a CtBP2-positive vesicle. Hair cells were intact other than the loss of ribbons (based on immunohistochemistry and DPOAE).

CONCLUSIONThese findings define the effect of SGN loss on the precise spatiotemporal size and location of ribbons and the time course of synaptic degeneration and provide a model for studying plasticity and regeneration.

Animals ; Female ; Hair Cells, Auditory ; cytology ; physiology ; Hair Cells, Auditory, Inner ; cytology ; physiology ; Mice ; Mice, Inbred CBA ; Synapses ; physiology

The influence of alpha-fetoprotein (AFP) on the bone marrow (BM) natural suppressor (NS) cells of intact Ehrlich carcinoma -bearing CBA mice was studied. Bone marrow NS cells were fractionated into three fractions by isopycnic centrifugation on percoll gradients: NS1 (rho=1.080 g/ml), NS2 (rho=1.090 g/ml) and NS3 (1.100>rho>1.090 g/ml). These fractions were highly different in their sensitivity to known NS cell inductors (interleukin (IL)-2, IL-3 or histamine). None of the NS fractions isolated from the intact mice spontaneously produced antiproliferative activity, however, they showed a high level of NS (antiproliferative and natural killer cell inhibitory) activity under the influence of AFP. A single injection of AFP to intact mice led to an increase of spontaneous NS activity and the inhibition of natural killer cell activity. NS activity, especially NS2, was increased in when tumor cells were subcutaneously inoculated three days after AFP injection. In the AFP-treated mice, the tumor mass at 14 days was 60% larger than that in the untreated mice. Our data confirmed that AFP is a tumor marker that can inhibit cancer immunity and plays a role in cancer pathogenesis.
alpha-Fetoproteins ; Animals ; Bone Marrow ; Centrifugation, Isopycnic ; Interleukin-3 ; Killer Cells, Natural ; Mice ; Mice, Inbred CBA ; Povidone ; Silicon Dioxide

AIMTo compare the thresholds of auditory brain-stem response (ABR) and frequency characteristics in five normal rodent species: CBA, BABL/c, C57BL, KunMing mice and guinea pigs.

METHODSAuditory brain-stem responses in four species of mice and guinea pigs were investigated with IHS-SmartEP 3.91 system. The thresholds and characteristics of ABR in each frequency were measured by the stimulated sound of tone-pip. Acoustic frequency-threshold curves in these five rodent species were made. The optimal response frequencies were assessed.

RESULTSThe thresholds of guinea pigs were the lowest in five rodent species, and KunMing mice, CBA mice, BALB/c mice, C57BL mice in turn. All the thresholds of ABR in these experimental animals were the lowest in 10 kHz. The thresholds became increasing in higher frequency (> 10 kHz), and in lower frequency (< 10 kHz). This was a common characteristic in frequency threshold curves of ABR in these five rodent species.

CONCLUSIONThe hearing of guinea pigs was the best in these five rodent species. The hearing of KunMing mice was sharper than those of the other mice. Stimuli of 10 kHz was the optimal frequency in these live rodent species, and the optimal frequency range was from 8 kHz to 24 kHz.

Acoustic Stimulation ; Animals ; Audiometry ; Auditory Threshold ; physiology ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Guinea Pigs ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Species Specificity

OBJECTIVES: Morphological studies on presbycusis, or age-related hearing loss, have been performed in several different strains of mice that demonstrate hearing loss with auditory pathology. The C57BL/6 (C57) mouse is a known model of early onset presbycusis, while the CBA mouse is characterized by relatively late onset hearing loss. We performed this study to further understand how early onset hearing loss is related with the aging process of the cochlea. METHODS: We compared C57 cochlear pathology and its accompanying apoptotic processes to those in CBA mice. Hearing thresholds and outer hair cell functions have been evaluated by auditory brainstem response (ABR) recordings and distortion product otoacoustic emission (DPOAE). RESULTS: ABR recordings and DPOAE studies demonstrated high frequency hearing loss in C57 mice at P3mo of age. Cochlear morphologic studies of P1mo C57 and CBA mice did not show differences in the organ of Corti, spiral ganglion, or stria vascularis. However, from P3mo and onwards, a predominant early outer hair cell degeneration at the basal turn of the cochlea in C57 mice without definitive degeneration of spiral ganglion cells and stria vascularis/spiral ligament, compared with CBA mice, was observed. Additionally, apoptotic processes in the C57 mice also demonstrated an earlier progression. CONCLUSION: These data suggest that the C57 mouse could be an excellent animal model for early onset 'sensory' presbycusis in their young age until P6mo. Further studies to investigate the intrinsic or extrinsic etiologic factors that lead to the early degeneration of organ of Corti, especially in the high frequency region, in C57 mice may provide a possible pathological mechanism of early onset hearing loss.
Aging ; Animals ; Apoptosis ; Cochlea ; Evoked Potentials, Auditory, Brain Stem ; Hair ; Hearing ; Hearing Loss ; Ligaments ; Mice ; Mice, Inbred CBA ; Models, Animal ; Organ of Corti ; Presbycusis ; Spiral Ganglion ; Stria Vascularis

To explore immune intervention effects of the combined use of cycloporin A (CsA) and 1, 25-dihydroxyvitamin D3[1,25(OH)2D3] at low doses on experimental autoimmune thyroiditis (EAT), porcine thyroglobulin (pTG) was injected into a CBA mouse at the dose of 100 micrograms on day 0 and day 14 to establish the model of EAT. The immune prevention group from day 0 to day 28, and treatment group from day 10 to day 38 were daily administered CsA (10 mg/kg) intragastrically and/or 1,25(OH)2D3 (0.2 microgram/kg) i.p. After immunized by pTG, the mice were sacrificed on day 28 and day 38 to examine their thyroid gland pathologically, and to check the levels of serum porcine thyroglobulin antibodies (pTGAb), porcine thyromicrosomal antibodies (pTMAb). The incidences of EAT in the immune prevention group and treatment group, with administration of low dose of CsA and 1,25(OH)2D3, were decreased respectively by 44.44% and 37.50%. Those of severe disease in the two groups were decreased respectively by 71.43% and 60.32%. The levels of serum pTGAb and pTMAb in the immune prevention group were lower than those of the positive control group. It was concluded that combined use of CsA and 1,25(OH)2D3 at low doses could effectively prevent EAT with a synergic effect.
Animals ; Antibodies ; blood ; Calcitriol ; therapeutic use ; Cyclosporine ; therapeutic use ; Drug Synergism ; Female ; Mice ; Mice, Inbred CBA ; Thyroglobulin ; immunology ; Thyroiditis, Autoimmune ; drug therapy ; immunology ; prevention & control