Wild Female Mice Research Articles

Antagonistic circuits mediating infanticide and maternal care in female mice.

In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state1,2. Naive wild female mice often kill pups, while lactating female mice are dedicated to pup caring3,4. The neural mechanisms that mediate infanticide and its switch to maternal behaviours during motherhood remain unclear. Here, on the basis of the hypothesis that maternal and infanticidal behaviours are supported by distinct and competing neural circuits5,6, we use the medial preoptic area (MPOA), a key site for maternal behaviours7-11, as a starting point and identify three MPOA-connected brain regions that drive differential negative pup-directed behaviours. Functional manipulation and in vivo recording reveal that oestrogen receptor α (ESR1)-expressing cells in the principal nucleus of the bed nucleus of stria terminalis (BNSTprESR1) are necessary, sufficient and naturally activated during infanticide in female mice. MPOAESR1 and BNSTprESR1 neurons form reciprocal inhibition to control the balance between positive and negative infant-directed behaviours. During motherhood, MPOAESR1 and BNSTprESR1 cells change their excitability in opposite directions, supporting a marked switch of female behaviours towards the young.

Stressfulness of the design influences consistency of cognitive measures and their correlation with animal personality traits in wild mice (Mus musculus)

Individual variation in cognition is being increasingly recognized as an important evolutionary force but contradictory results so far hamper a general understanding of consistency and association with other behaviors. Partly, this might be caused by external factors imposed by the design. Stress, for example, is known to influence cognition, with mild stress improving learning abilities, while strong or chronic stress impairs them. Also, there might be intraspecific variation in how stressful a given situation is perceived. We investigated two personality traits (stress coping and voluntary exploration), spatial learning with two mazes, and problem-solving in low- and high-stress tests with a group of 30 female wild mice (Mus musculus domesticus). For each test, perceived stress was assessed by measuring body temperature change with infrared thermography, a new non-invasive method that measures skin temperature as a proxy of changes in the sympathetic system activity. While spatial learning and problem-solving were found to be repeatable traits in mice in earlier studies, none of the learning measures were significantly repeatable between the two stress conditions in our study, indicating that the stress level impacts learning. We found correlations between learning and personality traits; however, they differed between the two stress conditions and between the cognitive tasks, suggesting that different mechanisms underlie these processes. These findings could explain some of the contradictory findings in the literature and argue for very careful design of cognitive test setups to draw evolutionary implications.

Dyslipidemia’s influence on the secretion ovarian’s steroids in female mice

Introduction: The synthesis ovarian’s steroids is a process thats depends on the supply of cholesterol. Objective: to evaluate the influence of dyslipidemia on the secretion ovarian’s steroids. Methodology: wild female mice were used (C57BL6) and LDL (LDLR-/-), which they were separated into 4 groups (n = 10): WTS: fed a standard diet; WTHL: fed a high-fat diet; KOS: fed a standard diet; KOHL: fed a high-fat diet. After 60 days, the estrous cycle was analyzed and after anesthetized, blood was collected for the to assess the lipid profile, glucose, plasma insulin level and HOMA index was calculated. In addition, plasma levels of C-reactive protein, estrogen and progesterone were determined. Results: The hyperlipidic diet in both the WTHL and the KOHL group generated hypercholesterolemia when compared to the WTS and KOS, respectively, with a decrease in HDLc, associated with an increase in CRP levels. Severe hypercholesterolemia in the KOHL group generated insulin resistance, marked by an increase in HOMAir. Food hypercholesterolemia in the WTHL group, food and genetics in the KOHL group, compared to their WTS and KOS controls, was definitive in reducing plasma levels of estrogen and progesterone. The genetic hypercholesterolemia associated with insulin resistance observed in the KOS and KOHL groups reduced the levels of progesterone, this reduction being more severe in the KOHL group, which had the highest HOMAir. Conclusion: dyslipidemia affected ovarian steroidogenesis in mice by means of oxidative stress, inflammation and insulin resistance and / or by decreasing HDL cholesterol levels.

Effects of moderate aerobic exercise on thoracic aortic remodeling of female LDL-receptor knockout ovariectomized mice

Menopause is a major factor involved in dyslipidemia increasing the risk of atherosclerosis which may be reversed by a routine of aerobic physical activity. Thus, this study aimed to analyze the effects of aerobic training on the thoracic aorta of female LDL-receptor knockout mice submitted to estrogen deprivation. Fifteen genetically modified female mice, knockout for the low-density lipoprotein receptor (LDL-Knockout group) were used as experimental groups and fifteen wild female mice (C57BL/6 J) were used as control groups. Animals were divided as (n = 5/per group): sedentary control (SC); sedentary control ovariectomized (SCO); trained control ovariectomized (TCO); LDL-Knockout sedentary (KS); LDL-Knockout sedentary ovariectomized (KOS); and LDL-Knockout trained ovariectomized (KOT). Immunohistochemical techniques for TIMP-1 and metalloproteinases 2 and 9 were used to evaluate thoracic aorta remodeling. Picrosirius stain was used to highlight the collagen fibers. Verhoff-Van Gienson was used for the quantitative analyses of elastic lamellae. Our results demonstrate a positive remodeling promoted by physical exercise in ovariectomized and dyslipidemic animals. However, further studies are needed including the evaluation of inflammatory markers present in dyslipidemia.

Two of a Kind or a Full House? Reproductive Suppression and Alloparenting in Laboratory Mice.

Alloparenting, a behavior in which individuals other than the actual parents act in a parental role, is seen in many mammals, including house mice. In wild house mice, alloparental care is only seen when familiar sibling females simultaneously immigrate to a male’s territory, so in the laboratory, when a pair of unfamiliar female wild mice are mated with a male, alloparenting does not occur because one female will typically be reproductively suppressed. In contrast, laboratory mice are assumed to alloparent regardless of familiarity or relatedness and are therefore routinely trio bred to increase productivity. Empirical evidence supporting the presence of alloparental care in laboratory mice is lacking. Albino and pigmented inbred mice of the strain C57BL/6NCrl (B6) and outbred mice of the stock Crl:CF1 (CF1) were used to investigate alloparenting in laboratory mice since by mating pigmented and albino females with albino males of the same stock or strain, maternal parentage was easily determined. We housed pairs (M:F) or trios (M:2F) of mice in individually ventilated cages containing nesting material and followed reproductive performance for 16 weeks. Females in trios were tested to determine dominance at the start of the experiment, and again 5 days after the birth of a litter to determine if a female’s dominance shifted with the birth of pups. Results showed a significant and expected difference in number of offspring produced by B6 and CF1 (p < 0.0001). Pigmented mice nursed and nested with albino pups and vice-versa, confirming empirical observations from many that group nesting and alloparenting occurs in unrelated laboratory mice. When overall production of both individual mice and cages was examined, reproductive suppression was seen in trio cages. Dominance testing with the tube test did not correlate female reproduction with female dominance in a female-female dyad. Due to the reproductive suppression noted in trios, on a per-mouse basis, pair mating outperformed trio mating (p = 0.02) when the measure was weaned pups/female/week. No infanticide was seen in any cages, so the mechanism of reproductive suppression in trio matings may occur before birth.

The role of pregnancy associated progenitor cells in the regeneration of injured maternal organs

Microchimeric fetal cells are present in the maternal body over a long period and thought to have the ability to colonize multiple tissues and organs. They are found in a wide range of maternal tissues affected with variety of diseases, thus, there is a possibility that they may contribute tissue repair and regeneration. To assess their possibility of use in regenerative medicine, we investigated whether fetal cells regenerate infracted maternal organs. We crossbred wild female mice with male transgenic mice, expressing enhanced green fluorescent protein (EGFP), and total hysterectomies were performed at the day 6 of pregnancies. On day 60 after the operations, the mice were injected with streptozotocin (STZ) to induce multiple organs injuries. We also created the ischemic organ injury model ; myocardial infarction model and cerebral infarction model. Detection and quantification of fetal cells were then attempted in a variety of maternal organs via a fluorescent microscope and quantitative PCR amplification of the gfp transgene. Fetal cells were detected only in maternal bone marrow before maternal organs injuries were induced, however, they were detected not only in bone marrow but also in the maternal injured organs. Histological analysis showed that differentiated fetal cells were observed and their morphological appearance was indistinguishable from their maternal counterparts. These results indicate that fetal cells sustained their population in the maternal bone marrow, may have contributed to the maternal tissue regeneration.

Limited variation in the major urinary proteins of laboratory mice

Individual variation in a specialised set of scent communication proteins, the major urinary proteins (MUPs), provides a genetic identity signature that underlies individual and kin recognition, and the assessment of heterozygosity in wild house mice. Here we examine the extent to which MUP variation is retained among 30 classical strains of laboratory mice from three main lineages (Castle, C57, Swiss). Normal wild-type variation in urinary MUP pattern appears to have been lost at an early stage in the derivation of the classical laboratory strains. All strains from the Castle and Swiss lineages shared the same “individual” MUP pattern, consistent with common ancestry from very few founders, while those from the C57 lineage shared a different pattern. Notably, individual variation in MUP pattern was no greater within the Swiss outbred ICR (CD-1) strain than typical for inbred strains. Total urinary protein concentration varied considerably between even closely related substrains, together with minor variation in the relative amount of each MUP isoform expressed, although the functional significance of such quantitative variation in MUP expression has yet to be established. Expression was 2–8 fold higher among males, while a MUP expressed by most male but not female wild mice was expressed by C57 males but variably among Castle and Swiss males and occasionally by females in some strains. The lack of normal variation in MUP patterns within and between strains has important implications for the use of laboratory mice in behavioural or neurophysiological research investigating social recognition or mate choice.

Female competition in wild house mice depends upon timing of female/male settlement and kinship between females

We assessed the effects of different situational or social determinants on the regulation of female–female competition. We carried out a laboratory study to examine aggression and reproductive success of pairs of wild female mice, Mus musculus domesticus spp., as a function of the timing of settlement of females relative to that of males and the genetic relatedness and familiarity between females (sibling versus nonsibling females). After a few days of cohabitation with a male, females were highly aggressive towards, and intolerant of, any intruder female, regardless of relatedness and familiarity. In this condition, monogamy was the resulting mating pattern in approximately 80% of cases. Conversely, pairs of females who made contact with each other at the same time, or prior to cohabitation with a male, showed comparatively little aggression and a high degree of reciprocal tolerance. Only in these latter conditions did genetic relatedness and familiarity between females influence their behavioural interactions and reproductive success. Although nonsibling pairs showed higher frequencies of aggressive interactions than siblings, polygyny resulted in 97% of cases. However, in most sibling groups both the females weaned young and had greater reproductive success than nonsiblings. Nonsibling females appeared to compete for reproduction through the inhibition of reproduction or infanticide. These findings suggest that the timing of male/female settlement in a deme determines the level of female competition, which, in turn, affects the resulting mating pattern. Only when females showed social tolerance did genetic relatedness and familiarity influence reproductive success.

Exploration and risk assessment in female wild house mice ( Mus musculus musculus) and two laboratory strains

In an evolutionary prospective, it is possible that female mice have a differential perception of novel events than male mice and use a different behavioural strategy for risk assessment. However, female mice are less studied than male mice in behavioural tests of emotional reactivity. The aim of the present study was to investigate how wild-derived female house mice differ from domesticated female mice in their risk assessment strategy. A total of 46 adult female mice, 14 BALB/c, 16 C57BL/6 and 14 Wild mice were tested in the Concentric Square Field (CSF), Open Field (OF) and Elevated Plus Maze (EPM) at three consecutive days. Parameters from all three tests were categorized according to their relevance to activity, exploration, approach–avoidance and use of open areas–shelter. Principal Component Analysis (PCA-SIMCA) of the animals' behaviour in the CSF arena was performed both for females alone and in comparison with earlier findings in male mice under the same test conditions. The results clearly show that female wild mice had a higher avoidance of open areas than the laboratory strains. There was also a trend indicating differences in exploration and approach–avoidance between female Wild and the laboratory strains. The multivariate test, CSF, was able to detect differences between Wild and laboratory strains in three (exploration, approach–avoidance, open–shelter) of the four functional categories measured. Wild female mice also had a higher frequency of rearing and grooming and a lower duration in the corridors in the CSF. Clear strain differences were found between BALB and C57BL in all tests where BALB generally had higher risk assessment and lower risk taking than C57BL. No general sex differences were found, however the sex differences were greater in Wild mice compared to the laboratory strains.

Behavioral profile of wild mice in the elevated plus-maze test for anxiety

Systematic observations of the defensive behavior of wild rodents have greatly informed the experimental study of anxiety and its neural substrates in laboratory animals. However, as the former work has been almost exclusively carried out in rats, few data are available concerning the reactivity of wild mice to standardized tests of anxiety-related behavior. In the present experiments, we employed ethological measures to examine the behavioral responses of a wild-derived population of house mice ( Mus musculus) in the elevated plus-maze. In direct comparisons with laboratory Swiss mice, male wild mice exhibited substantially elevated levels of exploratory activities and an overall “preference” for the open arms of the plus-maze. On re-exposure to the plus-maze, male wild mice showed further increases in open arm exploration, while Swiss mice showed a marked shift to the enclosed parts of the plus-maze. Tested over a single session, female wild mice also exhibited a profile of high open arm exploration, but showed levels of exploratory behaviors and locomotor activity similar to female Swiss counterparts. While exploratory patterns in wild mice show similarities to profiles seen in certain laboratory strains (e.g., BALB/c), wild mice displayed a number of additional behaviors that are unprecedented in plus-maze studies with laboratory mice. These included actual and attempted jumps from the maze, spontaneous freezing, and exploration of the upper ledges of the closed arms. Thus, while in conventional terms the behavior of wild mice was consistent with one of low anxiety-like behavior, the presence of these unique elements instead indicates a profile more accurately characterized by high reactivity and escape motivation. We discuss how the use of an ethological approach to measuring plus-maze behavior can support accurate interpretation of other exceptional profiles in this test, such as those possibly arising from phenotyping of transgenic and gene knockout mice.

Use of the MHC for mate choice in wild house mice (Mus domesticus).

The mechanisms maintaining natural diversity at the major histocompatibility complex (MHC) are not well understood. To increase knowledge of one potential mechanism, I examined the use of MHC genes for mate choice by wild house mice in a controlled laboratory setting. Three rearing groups of wild test mice were produced: non-fostered control mice, mice fostered into families of an inbred laboratory mouse strain, and mice fostered into families of a second, MHC-congenic mouse strain. Mature test mice were given a choice of two opposite-sex stimulus mice from the two MHC-congenic strains used for fostering, and were scored for several measures of preference. The results were non-significant in general, but females of two rearing groups spent significantly more time with mice of one MHC-type, and in most rearing groups, mice tended to spend more time with this same MHC-type. Other results showed that male test mice ejaculated indiscriminantly and that female wild mice mated to ejaculation more often in longer length trials, but showed no significant preferences. In this study, fostering seemed to have little or no effect on MHC-based mate preferences of wild house mice, and wild mice did not appear to be using the MHC to avoid inbreeding. However, some wild female mice used the MHC to choose potential mates.

The major histocompatibility complex and mating preferences in wild house mice (mus domesticus)

This study examined the relationship between the major histocompatibility complex (MHC) genes and mate choice by wild house mice in a controlled laboratory setting in an attempt to understand the mechanisms maintaining natural MHC diversity. Three rearing groups of wild test mice were produced: nonfostered control mice, mice fostered into families of an inbred laboratory mouse strain, and mice fostered into families of a second mouse strain differing genetically from the first only within the MHC region. At maturity, test mice were given a choice of two opposite-sex stimulus mice of the two MHC-congenic strains used for fostering. Test mice were scored for several measures of preference including amount of time spent with either stimulus mouse, and ejaculation with a stimulus mouse. Females in two of three rearing groups spent more time with one MHC type regardless of rearing environment, suggesting that females did not prefer mates dissimilar from family MHC type. Time preferences tended to be stronger in females than in males. Male test mice ejaculated indiscriminantly. Female wild mice mated to ejaculation more often in longer trials, but these matings were still too infrequent to assess preferences. Fostering had little or no effect on MHC-based mate preferences of wild house mice, and no evidence suggested that MHC was used to avoid inbreeding. Wild female mice may still choose mates based on MHC haplotypes (but do not necessarily prefer MHC-dissimilar mates); other cues are probably also used. Based on these results, inbreeding avoidance does not seem a strong mechanism for maintaining natural MHC diversity

Urine marking and maternal aggression of wild female mice in relation to anogenital distance at birth

A series of experiments were conducted with wild house mice to verify the effect of intrauterine position on females' anogenital distance at birth (AGD) and to examine the relationships between a female's AGD, used as a bioassay of androgen exposure during fetal life, and her social behavior and reproductive success in adulthood. Experiment 1 showed that cesarean-delivered females that developed in utero between two males (2 M females) have significantly longer AGD's than females positioned between two females (0 M females). We then categorized naturally delivered females shortly after birth as having a long, medium or short AGD. In adulthood, these females were tested for their behavior towards unfamiliar pups, their rate of urine-marking in response to a variety of social stimuli, postpartum aggression and success in protecting their litters in response to male and female intruders. Adult females with different AGD's at birth did not differ either in their behavior toward pups or in their rate of urine marking. Conversely, males housed across a wire mesh partition from a long-AGD female deposited a higher number of urine marks than those exposed to a short-AGE) female. When tested after delivering a litter, long-AGD females displayed more tail-rattling (a component of agonistic behavior) towards intruders of both sexes in comparison to short-AGD females. These results are consistent with the hypothesis that females with a long AGE) are exposed to higher levels of Testosterone during fetal life than females with a short AGD. Although not related to AGD, other measures of maternal aggression were affected by postpartum day, sex of intruders and a female's infanticidal potential while a virgin.

Male urinary cues stimulate intra-sexual aggression and urine-marking in wild female mice, Mus musculus domesticus

Male urinary cues stimulate intra-sexual aggression and urine-marking in wild female mice, Mus musculus domesticus

Maternal aggression toward infanticidal males of different social status in wild house mice (Mus musculus domesticus)

Maternal aggression was examined in wild female mice (Mus musculus domesticus) derived from animals trapped in Alberta, Canada. Lactating females were tested for their behavior toward intruder males during the time of postpartum estrus while housed in a two-cage apparatus containing a defensible nest area. Prior to being used as intruders, sexually naive males were screened for their behavior toward a newborn pup (83% exhibited infanticide). Only infanticidal males were then housed in pairs and allowed to establish a dominance hierarchy. Dominance status was further verified by a urine marking test. The dominant and subordinate infanticidal males were then placed into a lactating female's cage and observed for 1 hr. The test was terminated immediately when a male began to attack the pups. Lactating females attacked the males in both groups, but subordinate males received more intense attacks than dominant males. Dominant males elicited significantly more fear/defense behavior than subordinate intruders. All of the dominant males and only one submissive male attacked the pups. Females were thus successful in blocking infanticide only by infanticidal subordinate males. Since females do not persist in attacking males with high fighting ability, one function of maternal aggression could be to assess the fighting, and resource holding, potential of a future mate. © 1994 Wiley-Liss, Inc.

Determinants of the Synchrony of Reproduction in Townsend's Voles, Microtus townsendii

To determine whether synchronization of birth by female Townsend's voles occurs in natural populations as a result of environmental or social factors, the temporal pattern of reproduction was monitored in two populations of known relatedness. reproduction was most intense from April to July and less intense during the infestation by botflies in August and September. Synchronization of births was not related to the distance between females's nests or activity centers. This suggests that habitat characteristics of home-ranges do not cause the synchronization of parturitions. There was no correlation between the degree of relatedness of females and the synchronization of the birth of their litters. Among nearest neighbours, pairs of sisters and mothers and their daughters reproducing in the year of their birth had their litters significantly more synchronized than other females. Thus neighbouring relatives reproduce more synchronously than unrelated neighbours. Because related females often breed in communal home-ranges they could benefit from synchrony through a reduction of the risk of their pups being killed by close-relatives. Voles are thought to be unable to recognize their relative's offspring and it is possible that, like female wild mice, female Townsend's voles are infanticidal during pregnancy and non-infanticidal during lactation. The degree of synchrony of the spring onset of reproduction changed between years and was not higher among females of high average relatedness. Thus the synchrony of the onset of reproduction in spring is more a consequence of differences in the condition of individual females than determined by the extent of female territoriality.

Changes in incidence of infanticidal and parental responses during the reproductive cycle in male and female wild mice Mus musculus

Most studies of infanticide in rodents have been carried out on laboratory animals. In the present study, pairs of infanticidal male and female wild mice were observed for changes in their responsiveness to alien pups during the reproductive cycle. Females killed pups during pregnancy, adopted alien pups during the lactation period, and killed pups again a month after the weaning of their offspring. In males, the transition from infanticidal to parental responses occurred as early as the first half of their mates' pregnancy, and only half of them resumed infanticide a month after the weaning of their litters. Subsequent experiments showed that two independent factors, the experience of copulation and cues from the pregnant female, accounted for the cessation of infanticide and onset of parental care in the male. The adaptive value of the co-existence of multiple mechanisms underlying the cessation of infanticide in male and female house mice is discussed with respect to the social life of this species.

Infanticide and parental behavior in wild female house mice: Effects of ovariectomy, adrenalectomy and administration of oxytocin and prostaglandin F 2α

We have previously observed that about 60% of virgin, wild female house mice (Mus musculus), that were the offspring of wild mice trapped in Missouri, exhibited infanticide when a single 2-day-old pup was placed into each female's home cage. But, by the end of pregnancy, there was a significant increase (to 90%) in the proportion of wild female mice that exhibited infanticide. At parturition, infanticide was inhibited and parental behavior was induced in all females. In the present study we examined the influence of ovarian and adrenal hormones, as well as two hormones associated with pregnancy and parturition: oxytocin and prostaglandin F 2α (PGF), in regulating infanticide and parental behavior in wild female house mice. The presence or absence of gonadal and adrenal hormones did not influence the frequency of infanticidal behavior in adult female mice. Subcutaneous injections of either oxytocin or PGF inhibited infanticide in previously infanticidal pregnant females 1 hr after injection, but only oxytocin served to also facilitate parental behavior (most PGF-treated females left the pup untouched). Oxytocin, but not PGF, was effective in inhibiting infanticide in previously infanticidal virgin females. These findings suggest that, by themselves, ovarian and adrenal hormones do not mediate the exhibition of infanticide by wild female mice, but the lack of response to PGF in virgin females suggests that endocrine changes during pregnancy (possibly changes in steroids) may modulate the inhibitory effects of PGF on infanticide.

Selection for agonistic behavior in wild female mice.

This article reports the results of 11 generations of selective breeding for isolation-induced, interfemale aggression in Mus musculus. Within-family selection was used to form two high, two low, and two unselected control lines, beginning with a population of wild-trapped mice. Selection was successful in establishing the divergent lines, so that in recent generations about 50% of high-line animals attack, as do 25% of controls and 5% of lows. Realized heritabilities for eight generations of selection were 0.12 for H1, 0.14 for H2, 0.34 for L1, and 0.46 for L2. Male aggression has apparently not shown a correlated response to selection for female aggression. Group housing reduces the aggression of female mice, but the order of the lines is maintained under either isolation or group housing. Practical problems encountered in this selection program are discussed.

Types B and C RNA virus in breast tissue and milk of wild mice.

Type B virus particles were found by electron microscopy in prelactating breast tissue and milk samples from many recently trapped pregnant wild mice from 3 trapping areas in southern California. Type C virus particles and the corresponding complement-fixing group-specific (gs) antigen were found in low incidence in prelactating breast and spleen tissues of mice from 2 of these areas. However, wild mice from the third trapping area showed a high prevalence of type C particles and gs antigen in these tissues and type C particles in milk. An increased incidence of spontaneous breast tumors, as well as lymphomas, was observed in nonpregnant female wild mice from this third trapping area.