Survey of embryonic stem cell line source strains in the water maze reveals superior reversal learning of 129S6/SvEvTac mice

The availability of pluripotent embryonic stem (ES) cells for gene targeting has resulted in laboratory mice becoming important animal models of human neurological disease. Inbred strains of mice differ in many behavioural phenotypes, such that the same gene mutation can appear to have different phenotypic effects when introduced onto different genetic backgrounds. Prior knowledge of the behavioural phenotypes of the inbred strains used for gene targeting would, therefore, allow the selection of the most appropriate genetic background for the hypothesis to be tested. With this in mind, we tested eight strains of mice (129S1/SvImJ, 129S2/SvPasIcoCrlBR, 129S6/SvEvTac, B6129SF1/J, C57BL/6J, C57BL/6N, LP/J and SM/J), including the sources of five ES cell lines commonly used for gene targeting, in the spatial (submerged platform) version of the Morris water maze, the most widely used paradigm to evaluate the cognitive abilities of genetically modified mice. The three 129 substrain sources of ES cell lines demonstrated spatial learning in the water maze that was superior to that of C57BL/6J, the inbred strain most commonly used for the maintenance and phenotypic testing of mutations. In addition, 129S6/SvEvTac was unique amongst the eight strains tested in having a particular capacity for reversal learning, when the submerged platform was relocated to the opposite quadrant. We conclude that some substrains of 129 could provide suitable genetic backgrounds for testing gene mutations that might be expected to impair cognitive function, thus negating the need to backcross to C57BL/6J, thereby avoiding the so-called "flanking gene problem".     

Strain-dependent neurodevelopmental abnormalities in caspase-3-deficient mice

Targeted gene disruptions have revealed significant roles for caspase family members in the regulation of neuronal programmed cell death. Both caspase-3- and caspase-9-deficient mice exhibit a variably severe neurodevelopmental phenotype that may include marked ventricular zone expansion, exencephaly, and ectopic neuronal structures. Our previous studies of caspase-3- and caspase-9-deficient mice were performed using mice on mixed genetic backgrounds, raising the possibility that strain-specific generic factors influence the effects of caspase deficiency on nervous system development. To directly test this hypothesis. we backcrossed the caspase-3 mutation for 7-10 generations onto pure C57BL/6J and 129X1/SvJ genetic backgrounds. Caspase-3-deficient 129X1/SvJ mice were uniformly and severely affected. These mice died during the perinatal period and exhibited marked neural precursor cell expansion and exencephaly. In contrast, caspase-3-deficient C57BL/6J mice reached adulthood, were fertile and showed minimal brain pathology. Intercrosses of C57BL/6J and 129X1/SvJ mutants revealed that the vast majority of caspase-3-/- F1 mice displayed the severe 129X1/SvJ-"like" phenotype. These findings are consistent with an incompletely penetrant strain-dependent genetic modifier (or modifiers) that alters the neurodevelopmental consequences of caspase-3 deficiency. Since caspase-9- and Apaf-1-deficient mice also display variably severe developmental neuropathology, this strain-dependent modifier(s) may be involved in the activation of a caspase-independent death pathway; alternatively, strain-dependent compensatory caspase activation and/or its inhibition may influence the severity of the caspase-3-deficient neuronal phenotype.     

Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome

Fragile X syndrome results from inadequate production of the fragile X mental retardation protein (FMRP). Mice with a mutation targeted to the Fmr1 gene lack FMRP and thus are a valuable animal model for studying the behavioral and neural phenotype of this human disorder. Mice of two genetic backgrounds containing the Fmr1 mutation, C57BL/6J (C57-KO) and an F1 hybrid (C57BL/6J mutant x FVB/NJ; F1-KO) did not differ from control mice in behavior in the elevated plus maze or the open field. Both the C57-KO and F1-KO mice exhibited greater startle responses than normal mice to low intensity (80 dB) white noise bursts and decreased responses to high intensity (120 dB) white noise bursts. These behavioral alterations appear to be specific to the Fmr1 mutation since they are present on both genetic backgrounds. Furthermore, the mice lacking FMRP resemble individuals with fragile X syndrome in their increased sensitivity to low intensity auditory stimuli. These findings should prove useful in determining how the absence of FMRP alters the brain and behavior, and in testing potential treatments for fragile X syndrome.     

Differences in nociceptive behavioral performance between C57BL/6J, 129S6/SvEv, B6 129 F1 and NMRI mice

The interpretation of knockout and transgenic mouse studies in pain research critically depends on detailed knowledge of the performance profile of the background strains. Pain-related behavior was compared between four relevant mouse strains (C57BL/6J, 129S6/SvEv, B6 129 F1 and NMRI mice of both sexes) using an extended test battery that included an unusual variety of assays for thermal and mechanical acute nociception, and inflammatory and neuropathic pain. Strain- and gender-dependent differences were demonstrated in many of these nociceptive assays. Particularly, C57BL and 129 mice, which serve as the default genetic backgrounds for experiments in genetically altered mice, display quite different patterns of nociceptive performance. Compared to C57BL/6J mice, 129S6/SvEv animals are less sensitive to inflammatory pain conditions (thermal sensitivity after carrageenan subplantar injection; flinch behavior after formalin injection), while the opposite is observed in the neuropathic pain condition and the visceral pain model. These data may be of special interest for genetic studies, where issues related to the background phenotype may confound their interpretation.     

Strain differences in brain alpha2- and beta-adrenergic receptor binding in dystrophic mice

We have examined alpha 2-adrenergic [( 3H]-clonidine) and beta-adrenergic [( 3H]-dihydroalprenolol; DHA) binding in brain membranes from four different dystrophic mouse mutants: 129/ReJ-dy; 129 B6F1/J-dy; C57BL/6J-dy and C57BL/6J-dy2J. As shown previously, male 129/ReJ-dy mice have significantly fewer brain [3H]-DHA binding sites than their littermate controls. In marked contrast, the remaining three mutants showed no differences in [3H]-DHA binding when compared to their respective controls although there were inter-strain differences, e.g., C57BL/6J-dy2J mice have significantly fewer binding sites than the 129B6F1/J-dy mice. On the other hand, we saw no strain differences in alpha 2-binding. In one mutant, however, (129 B6F1/J-dy) we observed a 50% increase in alpha 2-binding sites compared to littermate controls. We conclude that weight loss or undernutrition may be an important factor in determining brain levels of adrenergic binding sites in dystrophic mouse brain.     

Assessing the effects of the 129/Sv genetic background on swimming navigation learning in transgenic mutants: a study using mice with a modified β-amyloid precursor protein gene

The Morris water maze is frequently used to screen mutant mice generated by gene targeting. Targeted ES-cells are often derived from 129/Sv or BALB/c mice, known as poor swimming navigation learners. After mating the founders with C57BL/6 mice, the F2 or F3 hybrid generation is typically used for behavioral testing. In hybrid 129/Sv×C57BL/6 mice, a modification of the βAPP gene entails impaired swimming navigation learning. This is readily detected despite behavioral variability, because wild-type 129/Sv×C57BL/6 hybrids outperform either of the parental strains and provide a control sample with good baseline performance. However, after backcrossing to the 129/Sv(ev) strain, the mutation effects are no longer detectable, masked by the very poor performance of wild-type 129/Sv(ev) mice. We conclude that F2 and F3 generations of 129/Sv×C57BL/6 crosses provide a suitable genetic background for behavioral testing of transgenic mice, provided that the samples are large enough to compensate for genetic and epigenetic variability and provided that normal performance in the control group is verified by comparison against a large database of mice tested under identical conditions. Creating congenic lines by backcrossing to an inbred strain is unlikely to enhance the sensitivity of the Morris test. Backcrossing to 129/Sv(ev) may even reduce it.     

Genetic background influences the behavioural and molecular consequences of neurokinin-1 receptor knockout

Genetic background affects animal phenotype and therefore is of particular relevance to studies using genetically manipulated mice. Strain differences in hypothalamic–pituitary–adrenocortical (HPA) axis activity may contribute to background-specificity of some mutations. Here, we analysed components of the HPA axis in mice lacking a functional neurokinin-1 receptor (NK1–/–) on two backgrounds: backcrossed C57BL/6 (B6) and mixed C57BL/6 × 129/sv (129B6). We hypothesized that HPA axis activity would vary between these strains, leading to differences in the NK1–/– phenotype. We compared levels of plasma corticosterone between the groups, and found 129B6 mice exhibited elevated levels of stress-induced corticosterone compared with B6 mice, regardless of genotype. Although the level of basal corticotrophin-releasing factor and stress-induced c-fos mRNAs did not differ between the genotypes of either strain, examination of glucocorticoid receptor immunoreactivity within the hippocampus revealed that NK1–/– mice on the 129B6 background had elevated expression compared with wild-type, whilst there was no difference between genotypes in the B6 strain. Similarly, hippocampal neurogenesis in NK1–/– mice was greater than in wild-type on the 129B6 strain, and did not differ between genotypes on the B6 background. Finally, novelty- and morphine-induced locomotion were assessed. NK1–/– mice on the 129B6 background exhibited hyperlocomotion in response to novelty and greater sensitivity to the locomotor-stimulating properties of morphine than wild-type. In contrast, in B6 mice, no differences were observed between genotypes for either locomotor behaviour. In summary, we find that HPA axis activity differs between the strains and that there are profoundly background-specific effects of the NK1 receptor mutation.     

Differential learning abilities of 129T2/Sv and C57BL/6J mice as assessed in three water maze protocols

Knockout mice are generated by using ES cells from 129 mouse strains and are frequently backcrossed with other strains, like C57BL/6. It is important to characterise the physiological and, in particular, the behavioural profile of each strain in order to correctly analyse the functional contribution of a single gene mutation on the 'cognitive' phenotype. The present study compared 129T2/Sv (129) and C57BL/6J (C57) mice in three different spatial learning protocols in the water maze, using a hidden platform. In the 'standard' reference memory protocol, 129 and C57 attained an equivalent level of performance as assessed by accuracy in reaching the platform (path length), despite a faster swim speed exhibited by C57 mice. In a stepwise learning task, C57 mice showed poorer performances over all stages of learning. However they performed better than 129 in a massed learning protocol which taxes short-term memory, and in which they exhibited lower levels of perseveration. The results emphasize the importance of using various tasks differing in cognitive demand, but using the same experimental environment and motivation, in order to 1) evaluate strain- or mutation-dependent learning abilities, and 2) dissociate the roles played by cognitive and non-cognitive factors in the behavioural requirements of the tasks.     

Attentional set-shifting in mice: modification of a rat paradigm, and evidence for strain-dependent variation

Increasingly precise molecular genetic tools are available to study in mice the cellular mechanisms underlying complex brain functions, but the behavioural paradigms to assess these functions often lack the required specificity. In this study, an attentional set-shifting paradigm to assess medial frontal cortex functions in rats was modified for use in mice and variation between two relevant mouse strains assessed. Male 129/SvEv and C57BL/6J mice and their F1 intercross (n=8 per genotype) were trained to dig in bowls for a food reward. On four consecutive days, mice performed a series of discriminations to criterion (six consecutive correct choices) between pairs of food bowls that differed along two dimensions (odour, digging medium), including a reversal, an intra-dimensional shift, and an extra-dimensional shift. Mice from the 129 strain performed significantly better than C57 mice in the initial acquisition of a simple discrimination and in the final extra-dimensional shift test, with no difference in the reversal and intra-dimensional shift. Performance of the F1 mice was intermediate or similar to that of the 129 mice. These results indicate a selective difference between these two strains in attentional selection processes that have been shown in humans, monkeys and rats to be mediated by prefrontal cortex.     

Lack of genotype effect on D1, D2 receptors and dopamine transporter binding in triple MOP‐, DOP‐, and KOP‐opioid receptor knockout mice of three different genetic backgrounds

We investigated D1, D2 receptors and dopamine transporter (DAT) binding levels in mice lacking all three opioid receptors and wild‐type (WT) mice on three different genetic backgrounds. Quantitative autoradiography was used to determine the level of radioligand binding to the D1 and D2 receptors and DAT labeled with [³H]SCH23390, [³H]raclopride, and [³H]mazindol, respectively in triple‐opioid receptor knockout (KO) and WT maintained on C57BL/6 (B6) and 129/SvEvTac (129) as well as C57BL/6 × 129/SvPas (B6 × 129) strains. No significant genotype effect was observed in D1, D2 receptors and DAT binding in any regions analyzed in any of the strains studied, suggesting that a lack of all three opioid receptors does not influence D1, D2 receptors and DAT expression, irrespective of their genetic strain background. However, strain differences were observed in D1 binding between the three strains of mice studied. Lower levels of D1 binding were observed in the substantia nigra of B6 × 129 WT mice compared with the 129 WT mice and in the olfactory tubercle of B6 × 129 WT compared with B6 WT and 129 WT mice. Lower levels of D1 binding were observed in the caudate putamen of B6 × 129 KO mice compared with 129 KO mice. In contrast, no significant strain differences were observed in D2 and DAT binding between the three strains of mice in any regions analyzed. Overall, these results indicate a lack of modulation of the dopaminergic system by the deletion of all three opioid receptors regardless of different background strains. Synapse 64:520–527, 2010. © 2010 Wiley‐Liss, Inc.     

Exploratory activity, motor coordination, and spatial learning in Mchr1 knockout mice

Male mice with a null mutation of Mchr1, encoding melanin concentrating hormone receptor-1, were compared to wild-type on two background strains. Mchr1 knockout (KO) mice were more active than 129/SvEv and C57BL/6J wild-type strains in a photocell actimeter. In addition, Mchr1 KO mice on the C57BL/6J background were less anxious in the elevated plus-maze, while on the 129/SvEv background, the mutants were less emotionally reactive as estimated by fecal boli and handling-related vocalization. There was no detrimental impact of the null mutation on motor coordination and spatial learning. Mchr1 KO mice had shorter latencies before reaching the escape platform, but only on the 129/SvEv background. Null mutants were lighter than C57BL/6J controls but heavier than 129/SvEv controls, attributable to interactions with strain-dependent genes.     

Central effects of a local inflammation in three commonly used mouse strains with a different anxious phenotype

As in humans, genetic background in rodents may influence a peculiar set of behavioural traits such as sensitivity to pain and stressors or anxiety-related behaviours. Therefore, we tested the hypothesis that mice with different genetic backgrounds [outbred (CD1), inbred (C57BL/6J) and hybrid (B6C3F1) adult male mice] display altered reactivity to pain, stress and anxiety related behaviours.We demonstrated that B6C3F1 mice displayed the more anxious phenotype with respect to C57BL/6J or CD1 animals, with the latter being the less anxious strain when tested in an open field and on an elevated plus maze. No difference was observed across strains in thermal sensitivity to a radiant heat source. Mice were then treated with a sub-plantar injection of the inflammatory agent Complete Freund's Adjuvant (CFA), 24 h later they were hyperalgesic with respect to saline exposed animals, irrespective of strain. We then measured intra-strain differences and CFA-induced inter-strain effects on the expression of various genes with a recognized role in pain and anxiety: BDNF, IL-6, IL-1β, IL-18 and NMDA receptor subunits in the mouse thalamus, hippocampus and hypothalamus. The more anxious phenotype observed in B6C3F1 hybrid mice displayed lower levels of BDNF mRNA in the hippocampus and hypothalamus when compared to outbred CD1 and C57BL/6J inbred mice. CFA led to a general decrease in central gene expression of the evaluated targets especially in CD1 mice, while BDNF hypothalamic downregulation stands out as a common effect of CFA in all three strains evaluated.     

Behavioural performance in three substrains of mouse strain 129

Recently, the possibility has been raised that the behavioural abnormalities seen in null-mutant mice might be determined by their genetic background rather than by loss of gene function, especially when the 129 mouse strain is used as supplier for embryonic stem (ES) cells. To examine this issue we tested three 129 mouse substrains (129/J, 129/Ola, 129/Sv-ter/+) and C57BL/6 (B6) in the Morris water maze, the open field, the plus maze and two tests assessing motor co-ordination. We identified only for the 129/J substrain substantial behavioural deficits. These mice are albinos and carry the pink-eyed dilution allele and differed in their basal anxiety level as assessed in the open-field test. They were severely impaired in spatial learning and memory (Morris water maze test), in the Porsolt swim test, which also measures learning and in motor co-ordination. However, the 129/J substrain has not been used as ES cell donor in null-mutant mice where behavioural abnormalities were observed. Instead, mice from 129/Ola and 129/Sv-ter/+ substrains have been commonly used as suppliers for ES cells. These performed normally in most of the tests, including Morris water maze test.     

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.     

Contrasting grooming phenotypes in C57Bl/6 and 129S1/SvImJ mice

Since C57 and 129 mice are the commonly used background strains, a better knowledge of all their behavioural characteristics is important in neuroscience research. Grooming is a complex and essential ritual in the rodent behavioural repertoire, normally proceeding in a cephalocaudal progression (paws-nose-face-body-legs-tail and genitals). Various stressors as well as genetic manipulations have been reported to alter mouse grooming and its patterning, underlying the importance of analysis of grooming behaviours in detail. Although strain differences between C57BL/6 and 129S1/SvImJ substrains have been assessed in many studies, no ethological analyses of their grooming have been performed. Here we show strain differences between these mice in spontaneous (novelty-induced) and artificial (water-induced) grooming. Overall, 129S1/SvImJ mice demonstrated less grooming activity, more interrupted and incomplete bouts, and more incorrect transitions (contrary to the cephalocaudal rule) between patterns, accompanied by lower vertical activity and higher defecation/urination in both tests. These results are consistent with general hypoactive anxious phenotype in 129S1/SvImJ mice and suggest that ethological analysis of mouse grooming may be used in neurobehavioural stress research, including behavioural phenotyping of both mutant and background mice.     

Neuroanatomy and psychomimetic-induced locomotion in C57BL/6J and 129/X1SvJ mice exposed to developmental vitamin D deficiency

Evidence from epidemiology suggests that developmental vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in rats is associated with altered brain morphology and enhanced hyperlocomotion in response to MK-801 and amphetamine. The aim of this study was to determine if similar phenotypes were associated with DVD deficiency in two strains of mice (C57BL/6J, 129/X1SvJ). Brains from neonatal (P0) and adult (P70) mice were imaged using MRI and the volumes of the cerebrum, hippocampus, striatum, septum, cortex and ventricles measured, as well as the widths of white matter tracts. Locomotor sensitivity to 5mg/kg d-amphetamine, 0.5mg/kg MK-801 or saline was examined in a separate group of mice in an open field. DVD deficiency altered brain morphology in C57BL6/J mice, such that C57BL/6J female DVD-deficient neonatal mice had a smaller hippocampus compared to female controls. In addition, adult C57BL/6J male DVD-deficient mice had smaller lateral ventricles compared to controls, which may have been compressed by the enlarged striatum seen in these DVD-deficient mice. However, in contrast to the behavioural phenotypes found in DVD-deficient rats, there was no significant effect of maternal diet on amphetamine or MK-801-induced locomotion in either strain. These data indicate that not only species, but also strain of mouse, moderates the impact of DVD deficiency on neuroanatomical and behavioural phenotypes in rodent animal models.     

Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury

Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp(-/-) mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models - a severe complete transection or a milder dorsal hemisection. OMgp(-/-) mice on the mixed 129BL6 genetic background showed greater functional improvement compared to OMgp(+/+) littermates, with increased numbers of cholera toxin B-labeled ascending sensory axons and 5-HT(+) descending axons and less RhoA activation after spinal cord injury. Myelin isolated from OMgp(-/-) mice (129BL6) was significantly less inhibitory to neurite outgrowth than wild-type (wt) myelin in vitro. However, OMgp(-/-) mice on a BL/6 genetic background showed neither statistically significant functional recovery nor axonal sprouting following dorsal hemisection.     

Visual capabilities and cortical maps in BALB/c mice

By combining behavioural analyses with intrinsic signal optical imaging, we analysed visual performance and visual cortical activity in the albino mouse strain BALB/c, which is increasingly being used as an animal model of neuropsychological disorders. Visual acuity, as measured by a virtual‐reality optomotor system, was 0.12 cycles per degree (cyc/deg) in BALB/c mice and 0.39 cyc/deg in pigmented C57BL/6 mice. Surprisingly, BALB/c mice showed reflexive head movements against the direction of the rotating stimulus. Contrast sensitivity was significantly lower in BALB/c mice (45% contrast at 0.064 cyc/deg) than in C57BL/6 mice (6% contrast). In the visual water task, visual acuity was 0.3 cyc/deg in BALB/c mice and 0.59 cyc/deg in C57BL/6 mice. Thus, the visual performance of BALB/c mice was significantly impaired in both behavioural tests – visual acuity was ～ 0.3 cyc/deg lower than in C57BL/6 mice, and contrast sensitivity was reduced by a factor of ～ 8. In BALB/c mice, visual cortical maps induced by stimulation of the contralateral eye were normal in both activation strength and retinotopic map quality. In contrast, maps induced by ipsilateral eye stimulation differed significantly between the strains – activity in a region representing 15° to 19° elevation in the visual field was significantly weaker in BALB/c mice than in C57BL/6 mice. Taken together, our observations show that BALB/c mice, like the albino animals of other species, have a significantly lower visual performance than C57BL/6 mice and a modified cortical representation of the ipsilateral eye that may impair stereopsis. Thus, our results caution against disregarding vision as a confounding factor in behavioural tests of neuropsychological disorders.     

Influence of genetic background and gender on bladder function in the mouse

Genetically targeted animals are used throughout research to investigate the role genes play in biological function, including the lower urinary tract. Generation of transgenic mice involves backcrossing for successive generations. Parental strain background genes can interact with the mutated gene potentially affecting interpretation of the mutant phenotype. Differences in physiological phenotypes may also be influenced by gender. The present study evaluated bladder function in five strains of male and female mice, 129S6/SvEvTac, A/J, B6129F1/Tac, BALB/cAnNCrL and C57BL/6NTacFBr. Urodynamic parameters were analyzed during infusion of saline (threshold and void volume, non-voiding contractions, pressure threshold and bladder contraction amplitude) in conscious mice and using voluntary urination in freely moving mice placed on filter paper (number of small and large diameter urine spots), which represent commonly used techniques in preclinical characterization of bladder function. Female BALB/c mice exhibited a significantly larger number of non-voiding contractions and urine dripping (increased number of small urine spots) compared to other female mice. Male BALB/c mice did not share this phenotype. Significant differences in threshold and void volumes were also noted amongst strains and genders. The numbers of large diameter urine spots differed amongst female, and not male, mouse strains. Gender differences were observed between sexes of the same strain in both large and small urine spots. These data demonstrate that genetic background and gender can influence bladder function in the mouse. These differences have a significant impact on the choice of strain and gender when investigating the effects of genetic manipulation on the micturition reflex.     

Anxiety responses, plasma corticosterone and central monoamine variations elicited by stressors in reactive and nonreactive mice and their reciprocal F1 hybrids

Stressor-provoked anxiety, plasma corticosterone, and variations of brain monoamine turnover are influenced by genetic factors, but may also be moderated by early life experiences. To evaluate the contribution of maternal influences, behavioral and neurochemical stress responses were assessed in strains of mice that were either stressor-reactive or -resilient (BALB/cByJ and C57BL/6ByJ, respectively) as well as in their reciprocal F(1) hybrids. BALB/cByJ mice demonstrated poorer maternal behaviors than did C57BL/6ByJ dams, irrespective of the pups being raised (inbred or F(1) hybrids). The BALB/cByJ mice appeared more anxious than C57BL/6ByJ mice, exhibiting greater reluctance to step-down from a platform and a greater startle response. Although the F(1) behavior generally resembled that of the C57BL/6ByJ parent strain, in the step-down test the influence of maternal factors were initially evident among the F(1) mice (particularly males) with a BALB/cByJ dam. However, over trials the C57BL/6ByJ-like behavior came to predominate. BALB/cByJ mice also exhibited greater plasma corticosterone elevations, 5-HT utilization in the central amygdala (CeA), and greater NE turnover in the paraventricular nucleus of the hypothalamus (PVN). Interestingly, among the F(1)'s corticosterone and 5-HIAA in the CeA resembled that of the BALB/cByJ parent strain, whereas MHPG accumulation in the PVN was more like that of C57BL/6ByJ mice. It seems that, to some extent, maternal factors influenced anxiety responses in the hybrids, but did not influence the corticosterone or the monoamine variations. The inheritance profiles suggest that anxiety was unrelated to either the corticosterone or monoamine changes.