Temperature preference differences between strains of Mus musculus,associated variables,and ecological implications

Summary Temperature preference differences were found between three inbred strains of mice, Balb/c having a lower preference than C3H and C57Bl. Hybrids with Balb/c had preferences between the inbred strains, while the C3HxC57Bl hybrid was close to the component inbred strains. Mice choosing low temperatures were heavier, had higher body temperatures and lower hair densities than those choosing high temperatures. Arguments are presented for regarding these associations as adaptive, and being morphological and physiological correlates of the behavioural measure temperature preference, a trait itself of ecological significance in habitat selection. It is considered that these traits are subjected to stabilizing selection for the optimum for a given population, to provide the most efficient habitat selection for that population.Tail length is not so intimately associated with temperature preference and shows overdominance in the direction of long tails unlike the other traits measured. In any case, published data show that while there is a general tendency for shorter tails to occur in environments with low temperatures and vice versa, this is not always true, so that tail length is not necessarily a good guide to the habitat selected.Mice were measured at two ages (15 to 18 days, and 55 to 58 days) for temperature preference, body weight and tail length. Developmental changes were found in that the preferred temperature was lower in the older mice. Furthermore, relative changes between age groups for all traits differed between some genotypes, indicating varying developmental changes according to genotype.     

Genetic analysis of various behavioral and physiologic characteristics in hybrids between hypertensive and normotensive rats. Analysis of correlational connections]

Hereditary links between different behavioral and physiological traits were studied in rat strains SHR, WKY and their hybrids F1 and F2 by analysis of correlations in segregating and nonsegregating gene-rations. Genetic correlation of arterial pressure with body mass, intake of KC1 solution and the ability to avoidance learning (directed positively) and with characteristics of exploratory activity (directed negatively) was shown. These traits seemed to be possible genetic markers of arterial hypertension. Genetical correlates of the ability to elaborate active avoidance conditional reaction (arterial pressure and pain sensitivity) testify to relief of active avoidance learning in animals with inherited active-defensive type of behaviour, manifested by predisposition to pressor reactions and by suppressed emotional reactions to pain stimulation. Frequency in intertrial crossings during avoidance training displays positive correlation with characteristics of exploratory behaviour. Positive correlation between different characteristics of exploratory activity was established both in segregating and nonsegregating generations.     

Strain differences in activity and emotionality do not account for differences in learning and memory performance between C57BL/6 and DBA/2 mice

This study examined emotionality, activity, learning and memory, as well as the influence of emotionality and activity on learning and memory performance in C57BL/6 and DBA/2 mice using a mouse-test battery. DBA/2 mice performed more poorly than C57BL/6 mice in complex learning tasks such as the water maze and object recognition tasks. In contrast, C57BL/6 mice showed attenuated habituation to novelty in the open field apparatus and poorer performance in the step-down passive avoidance task. The C57BL/6 mice were less exploratory and more anxious than the DBA/2 mice. The anxiety score (open arm entries in the elevated plus maze) was significantly correlated with all measures of learning and memory in the object recognition task, and some measures in the passive avoidance and water maze tasks. Analysis of covariance (with open arm entries as a covariate) revealed that some measures on trial 1 of the object recognition task, but not the memory scores on trial 2, were confounded by anxiety. No confounding factors of anxiety were found in the water maze or passive avoidance tasks. Similar results were obtained with the activity scores (line crossing and rearing in the open field). In conclusion, strain differences in activity and anxiety did not account for strain differences in learning and memory performance of C57BL/6 and DBA/2 mice. Nonetheless, the importance of using complete behavioural test batteries should be stressed to ensure that strain differences in learning and memory tasks are not confounded by non-cognitive factors.     

Lasting effects of early life stress in mice: interaction of maternal environment and infant genes

In the mouse, a powerful paradigm of early life stress, infant maternal separation (IMS), can trigger emotional and cognitive dysfunctions in adulthood similar to those found in humans with a history of childhood adversity. The magnitude of IMS effects differs among diverse inbred strains suggesting an interaction between the genetic background of pups and the maternal care they received. Here, we investigated this interaction with studies on reciprocal F1 hybrid mice of the stress‐susceptible Balb/c and the resilient C57Bl/6 strains that were either raised by Balb/c mothers (low maternal care) or by C57Bl/6 mothers (higher maternal care) with or without IMS exposure. The ultrasonic vocalization response to isolation was recorded from infant F1 pups, and their emotional, executive cognitive and epigenetic phenotypes were assessed in adulthood. These studies showed that, regardless of the maternal care received, the emotional phenotype of F1 hybrids was not significantly affected by IMS exposure. However, F1 pups raised by Balb/c (but not C57Bl/6) mothers during IMS exposure exhibit deficits in working memory and attention‐set‐shifting in adulthood. They also exhibit reduced histone deacetylase 1 levels at promotors of brain‐derived neurotrophic factor and early growth response 2 genes, and abnormally high induction of expression of these genes during cognitive testing. As one of affected genes was previously shown to associate with the Balb/c and the other with the C57Bl/6 genetic background, these findings indicate that both parental alleles interact with the maternal environment to modulate the cognitive and epigenetic phenotypes of F1 mice exposed to the IMS.     

Soluble factors in mouse immune sera: III. Origin,nature, and target of small molecular weight suppressive factors isolated from serum during primary responses

Small molecular weight suppressive factor (s) (< 10,000 daltons) were separated by Diaflo filtration from sera of Balb/c mice undergoing a primary response to sheep erythrocytes. These factors could be induced only when both T and B cells were challenged with antigen simultaneously. Thymus or bone marrow cells exposed in vitro to these factors showed marked impairment of their ability to collaborate for antibody synthesis in adoptive transfer experiments. These data suggest that both the T and B cells form the target for these factors. When the fractions showing suppressive activity were examined over a wide dose range, no enhancing activity was detected. The suppressive factors lost their activity after treatment with Pronase or heating at 63 °C for 30 min, but they were resistant to digestion with RNase.When a variety of mouse strains was examined for the production of small molecular weight suppressive factors it was found that certain strains produced factors which suppressed both 19 and 7S responses (Balb/cJ, AKR, and SJL/J), while in others factors affecting only the 7S response (A/J and C3H/He) or only the 19S response CBA/J) were detected. Finally, in some strains no suppressive activity was recovered (DBA/2 and B10D2), while in C57BL/6J distinct enhancing activity was detected. The F₁ hybrids of C57BL × Balb/c produced neither suppressive nor enhancing activity.     

Monogene inheritance of learning speed in DBA and C3H mice

Summary We carried out investigations on C3H, NMRI, C57B1/6, Balb/c, Balb/cN, and DBA inbred mouse strains in the shuttle-box to see whether their learning behavior is genetically controlled. The highly different learning behavior of the parental strains made it possible to test the F₁ hybrids and the F₂ generation. The environmental influences were standardized as much as possible. In particular, influences possible during the lactation period were excluded by using foster breeding. The results enable us to postulate monogenic inheritance for the learning speed in the shuttle-box. The inheritance is interpreted as codominant. The investigations are part of a basic study in mammalian behavior genetics from the human genetic aspect.     

The reactivity of the hypophyseal-adrenal system in rats with different forms of adaptive behavioral pathology]

The dexamethasone suppression test (DST) was applied to male Wistar rats with different models of depression: group with the learned helplessness, group with informational neurosis provided by time-deficit conditioned avoidance training, as well as groups of rats of two strains selected for low (KLA)--and high (KHA) avoidance learning. The pre-dexamethasone basal and stress-induced corticosterone levels were similar in intact rats and those exposed to inescapable shock. The dexamethasone administration (5 mkg/kg) failed to decrease the serum corticosterone level in rats with learned helplessness. The informational neurosis increased significantly the basal corticosterone level and decreased the stress response. Serum corticosterone levels were similar in KLA and KHA rats. These results give evidence that two stress-induced rat models of depression with similar behavioural disturbances (reduction of escape/avoidance reactions) exhibit marked differences in the activity of hypothalamo-pituitary-adrenal (HPA) axis.     

Isozymes of NADP-dependent isocitrate dehydrogenase in normal and tumor tissues of various mouse strains and their hybrids

Normal tissues of DBA, CBA, CC57W, C3H, Balb/c, SHR mice and F1 hybrids CC57W/DBA appeared to differ in the ratios of mitochondrial and supernatant NADP-dependent isocitrate dehydrogenase (IDH). Tested inbred mice strains CC57W, C3H, SHR, Balb/c contain allelic form Idh-1a of supernatant IDH gene Idh-1, whereas allelic form Idh-1b is characteristic of mice strains DBA and CBA. In tumors IDH isozymes have the same mobility as do isozymes of homologous normal tissues; but their activity is lower. A high variability of each isozyme activity in the isozyme spectrum is revealed in various tissues of F1 hybrids CC57W/DBA. Allelic forms of gene Idh-1 were used as markers of normal and tumor cells for the experimental model: transplantation of sarcoma 37 (Idh-1a/Idh-1a) to subcutaneous tissue of the mouse strain DBA (Idh-1b/Idh-1b). It enables us to reveal isozymes of stromal cell in tumor IDH isozyme spectrum. The results indicate that the relation of normal and tumor isozymes vary in different tumors.     

Hippocampal glucocorticoid receptor and behavior: a correlative study in rats and mice

A correlation has been demonstrated between binding capacity for [3H]corticosterone in the hippocampus and the performance in passive and active avoidance in the rat, and impaired behavior in adrenalectomized rats by exogenous corticosterone is restored. On this basis we have studied the possible correlation between strain-dependent behavioral differences and the glucocorticoid binding capacity in the hippocampus in mice and rats. In Naples high- (NHE) and low-excitability (NLE) rat strains, genetically selected on the basis of divergent locomotor activity upon forced exposure to a spatial novelty situation, no differences were found in glucocorticoid maximal binding capacity while both strains had a lower capacity than Naples random-breed (NRB) control rats. However, the intra-strain correlative analysis of hippocampal glucocorticoid receptors number and behavioral scores demonstrated that motor and emotional indexes of arousal to novelty were positively correlated in NLE-and negatively in NHE- while no correlation was present in NRB rats. Using two inbred strains of mice, C57BL/6 and Balb/c, extensively investigated for learning abilities, the lower active avoidance score of C57BL/6 was associated with a lower binding capacity for [3H]corticosterone in the hippocampus. Altogether the above results support the involvement of the hippocampal glucocorticoid receptor in the modulation of some adaptive behavioral responses, while do not prove that genetic differences in behavior rest on parallel differences in binding capacity for glucocorticoid hormone.     

Mouse liver and lung glutathione S-epoxide transferase: Effects of phenobarbital and 3-methylcholanthrene administration

The effects of 3-methylcholanthrene (3MC) and phenobarbital (PB) administration on the levels of glutathione-S-epoxide transferase activity in supernatant preparations of liver and lung were studied in a number of different strains of mice, C57Bl/6, C3H, C3H_f^?, Balb/c^?, A⁺ and DBA/2⁺. Three epoxide substrates, 3MC-11,12-oxide, styrene oxide (SO) and 3,3,3-trichloro-1,2-epoxypropane (TCPO), were employed in this investigation. PB administration (75 mg/kg body weight for 3 days) resulted in 13–57% increases in enzyme activity in the liver supernatant but was ineffective in inducing activity in lung. 3MC administration (40 mg/kg body weight for 2 days) on the other hand was without any effect on glutathione-S-epoxide transferase activity in both liver and lung.     

Relationship between genetic differentiation of the thymus in mice of different strains and malignant growth. IV. Genetic analysis of the thymic index in mice]

Relative thymus weight was estimated in C3H/He, C57BL/6 mice, their F1 and backcross hybrids, as well as in the progeny of complete diallel crosses between the BALB/c, C3H/He, C57BL/6 and AKR/J strains. On the basis of the analysis of these measurements, a conclusion is drawn that this character is inherited with incomplete dominance of smaller relative weight. The genes determining greater thymus weight are concentrated in the genetic pool of AKR/J and C57BL/6 strains. These genes are characterized by some degree of recessivity with respect to the genes determining smaller thymus weight which are concentrated in the genetic pool of C3H/He and BALB/c strains. The highest concentration of the "plus" and "minus" genes is found in the genetic pools of AKR/J and C3H/He strains respectively.     

Role of Cl-ionophore subunit in the functioning of GABA-benzodiazepine receptors

The displacement curves of the effect of picrotoxin on the S35-tert-butyl bicyclophosphorothionate binding to the brain membranes of inbred mice C57Bl/6 and Balb/c were analysed. The marked interstrain differences between modifications of IC50 and nHill dependent on the ionic force of the incubation medium were revealed. After partial stimulation of the receptor in the presence of 50 mM concentration of NaCl, the susceptibility of the receptor to picrotoxin was higher in the membrane suspension of C57Bl/6 mice than of Balb/c. Full stimulation of the receptor by 200 mM concentration of NaCl resulted in disappearance of interstrain differences. The value of nHill of C57Bl/6 membrane receptors increased after the change of the concentration of NaCl in the incubation medium from 50 to 200 mM, while it was invariable to Balb/c mice. It was marked that modification of the parameters of the binding of the radioligand to the membranes of C57Bl/6 mice was more latent, than for Balb/c mice.     

Analysis of the specific 3H-diazepam binding in the brain of inbred mice with differing emotionality

The influence of sodium chloride and gamma-aminobutyric acid (GABA) on H3-diazepam binding in CNS membrane fraction were investigated in C57Bl/6, BALB/c mice and their F1 hybrids. The addition of GABA (1, 10 and 100 microM) elevated the level of radioligand binding with CNS membranes in all the inbred mice in similar manner. The higher stimulating effect of sodium chloride (50, 100 and 150 mM) on the H3-diazepam reception was found in BALB/c mice and F1 hybrids, as compared to C57Bl/6 mice. It has been suggested that membrane-dependent conformational reconstructions of supramolecular receptor complex are the cause of genetic differences in the regulation of H3-diazepam reception by Cl(-)-ionophore.     

Behavioural profiles of inbred mouse strains used as transgenic backgrounds. II: cognitive tests

One of the characteristic manifestations of several neurodegenerative diseases is the progressive decline in cognitive ability. In order to determine the suitability of six mouse strains (129S2/Sv, BALB/c, C3H/He, C57BL/6j, CBA/Ca and DBA/2) as transgenic background strains, we investigated the performance on a variety of tasks designed to identify subtle changes in cognition. In addition, a test of exploratory behaviour was used to probe the level of underlying anxiety in these mouse strains, as anxiety can be a confounding factor on behavioural performance generally. The C3H/He mice exhibited the least anxiogenic behavioural profile spending most time on the open arms of the maze, in contrast to the 129S2/Sv mice which spent the least amount of time in this location and were the quickest to move into a closed arm. The C3H/He mouse strain failed to acquire a visual discrimination task and failed to demonstrate learning on a water maze spatial learning task, in contrast to the CBA/Ca, DBA/2 and C57BL/6j strains which demonstrated a degree of learning in both tasks. No significant strain differences were identified on the object recognition task. These data, taken together, suggest that care must be taken when choosing cognitive tasks to be used with particular mouse strains and that task sensitivity must be considered as a critical element to research protocols with regard to these mouse strains.     

Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study.

Aims of this study were to analyze the long-term effects of postovulatory aging of mouse oocytes on 1) reproductive traits of parental (F(0)) and first (F(1))-generation females (pregnancy rate, gestation length, litter size, perinatal death, and sex ratio of offspring) and 2) developmental and behavioral variables of F(1) and second-generation (F(2)) offspring (birth weight and weight gain during preweaning development, postnatal day of attainment of immediate righting, spontaneous motor activity, and passive and active conditioned learning ability). Hybrid (C57BL/6JIco x CBA/JIco) females were artificially inseminated at 13 h (control group) or 22 h (oocyte-aged group) after GnRH injection. Experimental (oocyte-aged group) F(0) females exhibited lower pregnancy rate, shortened gestation length, decreased litter size, higher perinatal death of their pups, and increased percentage of male offspring compared to control F(0) females. Postovulatory aging of oocytes was also associated with increased number of growth-retarded pups, delayed development of the righting reflex, and higher spontaneous motor activity and emotionality of F(1) offspring. Postovulatory aging of F(0) oocytes did not affect birth weight, weight gain during preweaning development, passive and active conditioned learning ability of F(1) offspring, or reproductive traits of F(1) females or developmental and behavior variables of F(2) offspring.     

In vitro spleen cell responsiveness to various analogs of MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine), a synthetic immunoadjuvant, in MDP high-responder mice

N-Acetylmuramyl-l-alanyl-d-isoglutamine (MDP), a synthetic immunoadjuvant, was incubated with spleen cells of DBA/2 or Balb/c mice and optimal responses were obtained after 4 or 5 days of culture in a serum-free medium supplemented with 2-mercaptoethanol. In contrast, lymphocytes of (C57B1/6 × AKR)F₁ hybrids responded weakly under the same conditions. The results reported here show that like in the case of DBA/2 and Balb/c strains, spleen cells of Swiss mice and of inbred AKR and CBA mice could be stimulated in vitro whereas C57B1/6 and LPS-refractory C3H/He mice did not respond. Fourteen synthetic MDP analogs (eight known to be adjuvant active and six devoid of activity) were tested in DBA/2 high-responder mice. A good correlation was observed between in vitro stimulation and the presence or absence of adjuvant activity in vivo of these compounds.     

Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains.

Angiogenesis is a critical element for adaptation to low levels of oxygen and occurs following long-term exposure to mild hypoxia in rats. To test whether a similar response in mice occurs, CD1, 129/Sv, C57Bl/6, and Balb/c mice were exposed to 10% oxygen for up to 3 wk. All mice showed significant increases in the percentage of packed red blood cells, and CD1 and 129/Sv mice showed increased respiration frequency and minute volume, common physiological measures of hypoxia. Significant angiogenesis was observed in all strains except Balb/c following 3-wk exposure to chronic hypoxia. CD1 hypoxic mice had the largest increase (88%), followed by C57Bl/6 (48%), 129/Sv (41%), and Balb/c (12%), suggesting that some mice undergo more remodeling than others in response to hypoxia. Protein expression analysis of vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and Ang2, and Tie2 were examined to determine whether regulation of different angiogenic proteins could account for the differences observed in hypoxia-induced angiogenesis. CD1 mice showed the strongest upregulation of VEGF, Ang2, Ang1, and Tie2, whereas Balb/c had only subtle increases in VEGF and no change in the other proteins. C57Bl/6 mice showed a regulatory response that fell between the CD1 and Balb/c mice, consistent with the intermediate increase in angiogenesis. Our results suggest that genetic heterogeneity plays a role in angiogenesis and regulation of angiogenic proteins and needs to be accounted for when designing and interpreting experiments using transgenic mice and when studying in vivo models of angiogenesis.     

The significance of the genotype and individual behavioral characteristics for the manifestation of the dominant phenotype in mouse micropopulations]

Influence of genotype and such individual characteristics as locomotor and exploratory activity, aggressiveness and emotionality, was studied in male mice. Males F1 and males of the parent line PT had high level of social dominance. F1 had high level of aggressiveness, and low emotionality, medium level of locomotor and exploratory activity. Significance of these individual behavioural characteristics for dominant behaviour is discussed.