OX40L在C57BL/6与BALB/c小鼠组织的差异性表达及分析

背景：有研究发现C57BL/6小鼠对动脉粥样硬化易感,而BALB/c小鼠却对动脉粥样硬化不易感。OX40L的表达情况与动脉粥样硬化的狭窄程度和心肌梗死的严重度相关,其在两种品系小鼠中是否存在表达差异？ 目的：分析OX40L在BALB/c和C57BL/6小鼠心脏、大脑、肾脏、骨骼肌和脾脏组织的表达差异。 方法：取C57BL/6和BALB/c小鼠心脏、大脑、肾脏、骨骼肌和脾脏组织,以Trizol提取总RNA, RIPA Buffer提取组织总蛋白。采用RT-PCR和Western Blot方法检测两种品系小鼠心脏、脑、肾脏、脾脏和骨骼肌的OX40L mRNA和蛋白的表达。OX40L在两种品系小鼠不同器官间的表达差异。 结果与结论：RT-PCR结果显示,C57BL/6小鼠心脏OX40L mRNA表达显著高于BALB/c小鼠(P < 0.05),脾脏OX40L mRNA表达明显低于BALB/c小鼠(P < 0.05),两种品系小鼠大脑、肾脏及骨骼肌OX40LmRNA表达差异无显著性意义;Western Blot结果显示,两种品系小鼠OX40L的蛋白表达均在心脏最高;C57BL/6小鼠心、脑及肾OX40L蛋白表达均显著高于BALB/c小鼠(P < 0.05),两种品系小鼠骨骼肌和脾脏OX40L蛋白表达差异无显著性意义。两个品系小鼠OX40L mRNA的表达水平与蛋白表达水平不完全一致。C57BL/6小鼠心脏中OX40L mRNA转录水平较BALB/c高,但在脾脏中表达量较后者低;C57BL/6小鼠心脏、大脑和肾脏OX40L蛋白水平均较BALB/c小鼠高;两种品系小鼠之间的表达差异提示OX40L可能与C57BL/6小鼠易感动脉粥样硬化有关。     

Genetic control of retinal projections in inbred strains of albino mice

Mutations in the tyrosinase gene are often associated with a misrouting of retinal ganglion cell axons at the optic chiasm. In albinos, tyrosinase activity is lost and some ganglion cell axons that would normally project into the ipsilateral optic tract instead cross midline and project into the contralateral tract. The developmental mechanisms that cause this modification in neuronal connectivity are unknown. In this study, we screened six diverse strains of albino mice (strains 129, A, AKR, BALB/c, C57BL/6-c/c, and CD-1) to discover genetically determined variations and possible gene loci that might affect the severity of the albino decussation abnormality. Ganglion cells were retrogradely labeled with horseradish peroxidase, and the ipsilaterally and contralaterally projecting cells were counted. The average number of ipsilaterally projecting ganglion cells in the six albino strains varies from 1,000 to 1,300. Despite this variation, 1.8–1.9% of the total population projects ipsilaterally in each strain. In comparison, 2.8% project ipsilaterally in the pigmented strain, C57BL/6-+/+. However, the percentage of displaced, ipsilaterally projecting cells varies substantially among albino strains-from a low of 4% in strain CD-1 to a high of nearly 10% in C57BL/6-c/c. We conclude that even with large differences in genetic background and in absolute numbers of ganglion cells, there is no appreciable variation in the magnitude of decussation error among albino mice. The consistent effect of null alleles at tyrosinase suggests a comparably tight linkage between the biochemical activity of this enzyme and the mechanisms that control decussation phenotype. © 1995 Wiley-Liss, Inc.     

The effect of neonatal N-methyl-D-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice

N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. In our study, we evaluated the effects of neonatal NMDA receptor blockade on exploratory locomotion and anxiety-like behaviors of adult BALB/c and C57BL/6 mice. In this study, NMDA receptor hypofunction was induced 7-10 days after birth using MK-801 in BALB/c and C57BL/6 mice (0.25mg/kg twice a day for 4 days via intraperitoneal injection). The open-field (OF) and elevated plus maze (EPM) tests were used to evaluate exploratory locomotion and anxiety-like behaviors. In the OF, BALB/c mice spent less time in the center of the field (p<0.05) and had less vertical locomotor activity (p<0.01) compared to C57BL/6 mice. In BALB/c mice, MK-801 caused a decrease in vertical and horizontal locomotor activity in the OF test, compared to the control group (p<0.05). In C57BL/6 mice, MK-801 treatment increased horizontal locomotor activity and decreased time spent in the center in the OF test (p<0.05). In the EPM, the number of open-arm entries, the percentage of open-arm time (p<0.01) and total arm entries (p<0.05) were lower in BALB/c mice compared to C57BL/6 mice. In BALB/c mice, MK-801 caused an increase in the percentage of open-arm time compared to the control group (p<0.05). In C57BL/6 mice, MK-801 caused a decrease in the percentage of open-arm time compared to the control group (p<0.05). MK-801 decreased exploratory and anxiety-like behaviors in BALB/c mice. In contrast, MK-801 increased exploratory and anxiety-like behaviors in C57BL/6 mice. In conclusion, hereditary factors may play an important role in neonatal NMDA receptor blockade-induced responses.     

Optical measurement of mouse strain differences in cerebral blood flow using indocyanine green

C57BL/6 mice have more cerebral arterial branches and collaterals than BALB/c mice. We measured and compared blood flow dynamics of the middle cerebral artery (MCA) in these two strains, using noninvasive optical imaging with indocyanine green (ICG). Relative maximum fluorescence intensity (I_max) and the time needed for ICG to reach I_max in the MCA of C57BL/c were lower than that in BALB/c mice. Moreover, the mean transit time was significantly lower in C57BL/6 than in BALB/c mice. These data suggest that the higher number of arterial branches and collaterals in C57BL/6 mice yields a lower blood flow per cerebral artery.     

Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains

Detailed characterisation of six inbred strains of mice commonly used in transgenic and knockout research was carried out using a battery of behavioural tests (SHIRPA) followed by discriminant analysis of the data. In the primary observation screen, DBA/2 mice were relatively irritable and vocalised during handling. C57BL/6 were hyperactive as measured by transfer arousal, arena activity and touch-escape tests. By contrast, C3H were markedly hypoactive, had significantly enhanced grip strength and were also significantly impaired on the visual placing task. In the elevated plus-maze, BALB/c mice showed the highest level of open arm entries and time spent in the open arms, indicating the lowest level of anxiety. There was a clear dissociation of strains on exploratory activity, as measured in the holeboard test and spontaneous locomotor activity (LMA). DBA/2 mice were hyperactive in LMA but demonstrated relatively low levels of holeboard exploration. None of the six strains learnt the water maze spatial learning task particularly well. C57BL/6 and 129/Sv demonstrated most ability and C3H showed no evidence of having acquired the task. The SHIRPA screening battery and discriminant analysis of the data have enabled us to determine the relevant contribution of a number of behavioural measurements to the marked differences in phenotype of mouse strains. These data confirm the importance of carrying out a comprehensive profile in order to accurately characterise the phenotype of gene-targeted and transgenic mice.     

Sexual differences and estrous cycle in methamphetamine-induced dopamine and serotonin depletions in the striatum of mice

Summary. Four consecutive doses (10 mg/kg) of methamphetamine, s.c., produced a substantial striatal dopamine depletion in both sexes of BALB/c and C57BL/6J mice. Male C57BL/6J mice exhibited greater dopamine depletions in the striatum compared to female C57BL/6J mice. In contrast, male and female BALB/c mice demonstrated an equivalent magnitude of striatal dopamine depletion. Regardless of sex, C57BL/6J mice demonstrated approximately 1.4 to 2.2 times greater dopamine depletions in the striatum compared to BALB/c mice. Moreover, methamphetamine caused 4 times greater serotonin depletions in male as opposed to female BALB/c mice while sparing either sex of the C57BL/6J mice. Furthermore, female mice of both strains appeared to have the greatest basal dopamine levels during proestrus and the lowest basal dopamine levels during diestrus. Likewise, female mice of both strains exhibited the lowest dopamine depletions in the striatum when the dosing regimen of methamphetamine started at proestrus whereas the greatest dopamine depletions in the striatum occurred when the regimen started during diestrus. These results suggest that sex hormones and other modulating factors may play a role in methamphetamine-induced dopamine and serotonin neurotoxicity. Received August 3, 1999; accepted September 13, 1999     

Corticosterone facilitates extinction of fear memory in BALB/c mice but strengthens cue related fear in C57BL/6 mice

Corticosterone, the naturally occurring glucocorticoid of rodents is secreted in response to stressors and is known for its facilitating and detrimental effects on emotional learning and memory. The large variability in the action of corticosterone on processing of emotional memories is postulated to depend on genetic background and the spatio-temporal domain in which the hormone operates. To address this hypothesis, mice of two strains with distinct corticosterone secretory patterns and behavioural phenotype (BALB/c and C57BL/6J) were treated with corticosterone (250 μg/kg, i.p.), either 5 min before or directly after acquisition in a fear conditioning task. As the paradigm allowed assessing in one experimental procedure both context- and cue-related fear behaviour, we were able to detect generalization and specificity of fear. BALB/c showed generalized strong fear memory, while C57BL/6J mice discriminated between freezing during context- and cue episodes. Corticosterone had opposite effects on fear memory depending on the strain and time of injection. Corticosterone after acquisition did not affect C57BL/6J mice, but destabilized consolidation and facilitated extinction in BALB/c. Corticosterone 5 min before acquisition strengthened stress-associated signals: BALB/c no longer showed lower fear memory, while C57BL/6J mice displayed increased fear memory and impaired extinction in cue episodes. We propose that corticosterone-induced facilitation of fear memory in C57BL/6J mice can be used to study the development of fear memories, corticosterone administration in BALB/c mice presents a model to examine treatment. We conclude that genetic background and time of corticosterone action are modifiers of fear memory with interesting translational implications for anxiety-related diseases.     

Effect of amantadine on motility of reserpinized mice as a function of brain biogenic amines and mouse strains

The effect of amantadine, reserpine or both on locomotor activity and whole brain content of selected biogenic amines and major metabolites was studied as a function of mouse strain. Successive administration of small dose regimens of reserpine, 0.2 mg/kg IP, did not alter motility from corresponding saline control. Administration of amantadine, 100 mg/kg, IP, prior to each of the reserpine treatments produced either stimulation of motor activity in the albino ICR and black C57BL/6 mice or caused inhibition from reserpine in the albino BALB/C and the brown CDF-1 mouse strains. This suggests a genotype strain sensitivity to the amantadine and reserpine interaction on the motor behavior of the mouse. The amantadine treatment did not alter brain dopamine concentration but increased its immediate acid metabolite, 3,4-dihydroxyphenylacetic acid, in the C57BL/6 mice as contrasted with reduction of the same in the BALB/C mouse strain. Both BALB/C and C57BL/6 mice showed changes in brain normetanephrine levels as a consequence of the pharmacologic intervention used which suggest catecholaminergic sensitivity. The only changes produced by the agents studied in brain serotonin or 5-hydroxyindoleacetic acid levels were confined to the BALB/C mouse strain. No changes occurred in brain levels of the compounds measured from corresponding controls in the CDF-1 mice. The results indicate differential sensitivity of the serotonergic and dopaminergic systems to drug-drug interaction studied which appears to be strain dependent.     

Genetic studies of daily variations of first-step enzymes of monoamines metabolism in the brain of inbred strains of mice and hybrids. II. Daily variations of tyrosine hydroxylase activity in the locus coeruleus

Daily variations of tyrosine hydroxylase (TH) activity in the locus coeruleus of 3 inbred strains of mice (BALB/c; C57BL6; C57Br) and of the F₁ hybrids obtained from BALB/c and C57BL/6 are discussed. Precise characteristics of the circadian rhythms were observed in each strain. They were found significantly different in two genetically pure parents (BALB/c and C57BL6). In their two F₁ hybrids the daily variation of TH activity was similar to that observed in one of the parents (C57BL6). This strongly suggests selective and genetically controlled mechanisms of regulation responsible for the daily variation of TH activity in the locus coeruleus of mice.     

Anxiety-related behaviour in C57BL/6 <--> BALB/c chimeric mice

In a previous study on anxiety-related behaviours of the genetically and behaviourally distant inbred mouse strains C57BL/6 and BALB/c using the Elevated plus-maze (EPM) and Open-field (OF) apparatuses, we identified a number of variables, the factorial scores of which were grouped by principal component analysis (PCA) into factors specifically describing each inbred strain [4]. We have now studied the effect of C57BL/6 and BALB/c haploid sets of genes on this behaviour by comparing EPM and OF variables of C57BL/6 and BALB/c versus C57BL/6×BALB/c F1 hybrids (B6CBF1) and chimeric C57BL/6×BALB/c (CHIM) mice. CHIM mice were made by embryo aggregation and the chimerism degree of their brain was inferred from coat black/white distribution. Discriminant analysis of EPM and OF factorial scores of C57BL/6, BALB/c and CHIM mice showed that CHIM mice with an exceeding (≥80%) C57BL/6 or BALB/c coat component had behaviours similar to those of the predominant strain, whereas CHIM mice with intermediate chimerism differed from both inbred strains. Additional MANOVA analysis showed that the anxiety behaviour of CHIM mice with intermediate chimerism was similar to that of B6CBF1 mice as for factors not describing the inbred strains, including a motor activity mostly limited to protected areas, with attempts to approach the anxiogenic areas while processing/storing the external information. We conclude that the balanced presence of both C57BL/6 and BALB/c genetic backgrounds, either when carried by the same cell or by different cells, gives rise to a novel stress coping strategy described by factors different from those of the inbred strains.     

Development of a model of seizure-induced hippocampal injury with features of programmed cell death in the BALB/c mouse

Although mice are amenable to gene knockout, they have not been exploited in the setting of seizure-induced neurodegeneration due to the resistance to injury of key mouse strains. We refined and developed models of seizure-induced neuronal death in the C57BL/6 and BALB/c strains by focally evoking seizures using intra-amygdala kainic acid. Seizures in adult male BALB/c mice, or C57BL/6 mice as reference, caused ipsilateral death of CA1 and CA3 neurons within the hippocampus. Termination of seizures by lorazepam was more effective than diazepam in both strains, largely restricting neuronal loss to the CA3 sector. Electroencephalography (EEG) recordings defined injurious and non-injurious seizure patterns, which could not be separated adequately by behavioral observation alone. Degenerating neurons in the hippocampus were positive for DNA fragmentation and approximately a third of these exhibited morphologic features of programmed cell death. Western blot analysis revealed the cleavage of caspase-8 after seizures in both strains. These data refine our C57BL/6 model and establish a companion model of focally evoked limbic seizures in the BALB/c mouse that provides further evidence for activation of programmed cell death after seizures.     

Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice

The relations between open-field, elevated plus-maze, and emergence tests were examined in two strains of mice. In the open-field, C57BL/6J mice had more ambulatory movements and rears but not stereotyped movements relative to BALB/c. In addition, C57BL/6J mice entered more often than BALB/c into enclosed and open arms of the elevated plus-maze. When placed inside a large enclosure, C57BL/6J mice emerged more quickly than BALB/c from a small toy object. In the entire series of mice, ambulation and rears in the open-field were linearly correlated with open and enclosed arm visits in the elevated plus-maze. Ambulatory movements and rears were also correlated with emergence latencies. In contrast, stereotyped movements were correlated with emergence latencies, but not with any elevated plus-maze value. These results specify the extent and limits of association between the three tests.     

Strain-dependent differences in hippocampal glucocorticoid binding capacity and active avoidance in the mouse

Maximal individual [3H]corticosterone binding capacity in the hippocampus was lower in C57BL/6 mice than in BALB/c mice, and positively correlated with active avoidance learning in the two strains. Moreover, a parallel difference in the activity of hypothalamo-pituitary adrenocortical axis (HPAA) was found, consisting in a level of plasma corticosterone in C57BL/6 higher than in BALB/c mice. These results confirm the genetically determined differences in behavior of C57BL/6 and BALB/c mice, and demonstrate their association with differences in hippocampal corticosterone binding capacity, pointing to a functional relationship between the behavioral and neuroendocrine parameters.     

Eye-specific projections of retinogeniculate axons are altered in albino mice

The divergence of retinal ganglion cell (RGC) axons into ipsilateral and contralateral projections at the optic chiasm and the subsequent segregation of retinal inputs into eye-specific domains in their target, the dorsal lateral geniculate nucleus (dLGN), are crucial for binocular vision. In albinism, affected individuals exhibit a lack or reduction of pigmentation in the eye and skin, a concomitant reduced ipsilateral projection, and diverse visual defects. Here we investigate how such altered decussation affects eye-specific retinogeniculate targeting in albino mice using the C57BL/6 Tyr(c-2J/c-2J) strain, in which tyrosinase, necessary for melanogenesis, is mutated. In albino mice, fewer RGCs from the ventrotemporal (VT) retina project ipsilaterally, reflected in a decrease in cells expressing ipsilateral markers. In addition, a population of RGCs from the VT retina projects contralaterally and, within the dLGN, their axons cluster into a patch separated from the contralateral termination area. Furthermore, eye-specific segregation is not complete in the albino dLGN and, upon perturbing postnatal retinal activity with epibatidine, the ipsilateral projection fragments and the aberrant contralateral patch disappears. These results suggest that the defects in afferent targeting and activity-dependent refinement in the albino dLGN arise from RGC misspecification together with potential perturbations of early activity patterns in the albino retina.     

The recruitment of peripheral blood leukocytes to the brain is delayed in susceptible BALB/c compared to resistant C57BL/6 mice during herpes simplex virus encephalitis

Journal of NeuroVirology - The cerebral immune response induced by herpes simplex virus (HSV) encephalitis (HSE) was evaluated in susceptible BALB/c and resistant C57BL/6 mice. BALB/c and C57BL/6...     

Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent

A new spontaneous mouse mutation named fierce (frc) is deleted for the nuclear receptor Nr2e1 gene (also known as Tlx, mouse homolog of Drosophila tailless). The fierce mutation is genetically and phenotypically similar to Nr2e1 targeted mutations previously studied on segregating genetic backgrounds. However, we have characterized the fierce brain, eye, and behavioural phenotypes on three defined genetic backgrounds (C57BL/6J, 129P3/JEms, and B6129F1). The data revealed many novel and background-dependent phenotypic characteristics. Whereas abnormalities in brain development, hypoplasia of cerebrum and olfactory lobes, were consistent on all three backgrounds, our novel finding of enlarged ventricles in 100% and overt hydrocephalus in up to 30% of fierce mice were unique to the C57BL/6J background. Developmental eye abnormalities were also background-dependent with B6129F1-frc mice having less severe thinning of optic layers and less affected electroretinogram responses. Impaired regression of hyaloid vessels was observed in all backgrounds. Furthermore, retinal vessels were deficient in size and number in 129P3/JEms-frc and B6129F1-frc mice but almost entirely absent in C57BL/6J-frc mice. We present the first standardized behavioural tests conducted on Nr2e1 mutant mice and show that C57BL/6J-frc and B6129F1-frc mice have deficits in sensorimotor assays and are hyperaggressive in both sexes and backgrounds. However, C57BL/6J-frc mice were significantly more aggressive than B6129F1-frc mice. Overall, this extensive characterization of the fierce mutation is essential to its application for the study of behavioural, and brain and eye developmental disorders. In addition, the background-dependent differences revealed will enable the identification of important genetic modifiers.     

Strain differences in the magnitude of swimming-induced analgesia in mice correlate with brain opiate receptor concentration

Swimming-induced analgesia was studied in 4 strains of mice differing in central opiate receptor density: C57BL/6By (C57), BALB/cBy (BALB/c), CXBK and CXBH. The degree of 'swim analgesia' significantly differed among strains in the order CXBH greater than BALB/c = C57 greater than CXBK. This order positively correlates with known differences in opiate receptor density in these strains. Naloxone reversed the analgesic effect of swimming in CXBH, C57 and BALB/c, but was ineffective in opiate receptor-deficient CXBK mice. These results suggest that genetic differences in central opiate receptor density influence the analgesic response to stressful stimuli.     

Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury

Susceptibility to neuroinflammatory disease is influenced in part by genetics. Recent data indicate that survival of traumatized neurons is strain dependent and influenced by polygenic loci that control resistance/susceptibility to experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmune disease. Here, we describe patterns of neurodegeneration and intraparenchymal inflammation after traumatic spinal cord injury (SCI) in mice known to exhibit varying degrees of EAE susceptibility [EAE-resistant (r) or EAE-susceptible (s) mice]. Spinal cords from C57BL/6 (EAE-s), C57BL/10 (EAE-r), BALB/c (EAE-r), and B10.PL (EAE-s) mice were prepared for stereological and immunohistochemical analysis at 6 hours or 3, 7, 14, 28, or 42 days following midthoracic (T9) spinal contusion injury. In general, genetic predisposition to EAE predicted the magnitude of intraparenchymal inflammation but not lesion size/length or locomotor recovery. Specifically, microglia/macrophage activation, recruitment of neutrophils and lymphocytes, and de novo synthesis of MHC class II were greatest in C57BL/6 mice and least in BALB/c mice at all times examined. However, lesion volume and axial spread of neurodegeneration were similar in C57BL/6 and BALB/c mice and were significantly greater than in C57BL/10 or B10.PL mice. Strains with marked intraspinal inflammation also developed the most intense lesion fibrosis. Thus, strain-dependent neuroinflammation was observed after SCI, but without a consistent relationship to EAE susceptibility or lesion progression. Only in C57BL/6 mice was the magnitude of intraspinal inflammation predictive of secondary neurodegeneration, functional recovery, or fibrosis.     

Conditioned enhancement of skin allografts in mice

Healthy A/J mice grafted with either BALB/c or C57BL/6 tail skin routinely reject these grafts with a mean survival time (MST) of 12-14 days. Low dose cyclophosphamide, Cy (50 mg/kg) on the day of engraftment can enhance survival of both grafts (MST 17-20 days). If mice are given three weekly intravenous injections of BALB/c peripheral blood prior to grafting, specific enhancement of BALB/c but not C57BL/6 grafts results (MST 18 and 12 days, respectively). Mice given several ip treatments with Cy in association with a novel taste (saccharin, Sacc) in their drinking water also show a conditioned immunosuppression if subsequently exposed to Sacc alone. Such mice given BALB/c or C57BL/6 skin grafts and re-exposed to Sacc also show prolonged survival of these skin allografts (MST 16-17 days). If conditioned mice are also treated, by pretransplant donor-specific transfusion, to develop a state of specific suppression of allograft immunity, then subsequent grafting with BALB/c or C57BL/6 grafts coupled with re-exposure to Sacc lead to a further prolonged survival of grafts specifically in the BALB/c mice (MST 29 days).     

品系和性别对小鼠甲醛实验的影响

目的 研究品系和性别等因素对小鼠甲醛实验的影响,为选择敏感、有效的小鼠疼痛模型提供可靠的实验参考.方法 在相同的实验条件下,通过给予不同品系、性别的昆明、BALB/c和C57BL/6小鼠右脚爪注射5％的甲醛溶液,记录并分析小鼠在甲醛实验早(0～5min)、晚(20～60 min)时相每5分钟的舔咬爪时间.结果 (1)在甲醛实验早时相,各观测时间点不同品系小鼠舔咬爪时间均无差异,而在晚时相:雄性昆明小鼠25～30 min的舔咬爪时间(23.25±17.27)s明显少于C57BL/6小鼠(63.33±18.20)s;雌性昆明小鼠在20～25 min舔咬爪时间(64.63±52.71)s较BALB/c小鼠(17.00±22.34)s和C57BL/6小鼠(32.17±27.42)s显著增多;C57BL/6小鼠在50～55 min舔咬爪时间(0.83±1.33)s明显比昆明小鼠(47.50±51.03)s少;(2)不同性别的小鼠甲醛实验表明,BALB/c小鼠雌雄间各观测时间点均没有显著差异.雄性昆明小鼠在25～30min的舔咬爪时间(23.25±17.27)s明显少于雌性(64.63±52.71)s;雄性C57BL/6小鼠在25～30 min的舔咬爪时间(63.33±18.20)s明显长于雌性(22.83±18.41)s.结论 品系和性别因素对小鼠甲醛实验有明显影响,为增加稳定性宜选择雄性近交系小鼠(BALB/c和C57BL/6)进行实验.