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Testicular regression in response to food restriction and short photoperiod in white-footed mice (Peromyscus leucopus) is mediated by apoptosis.

Short day lengths or reduced food availability are salient cues for small mammals that breed seasonally. Photoperiod-mediated gonadal regression in white-footed mice (Peromyscus leucopus) is a slow, orderly process that involves testicular apoptosis. Testicular regression in response to restricted caloric intake is relatively rapid, and it is generally reversed quickly by ad libitum (ad lib) feeding. To determine the contribution of apoptotic cell death during food restriction, and to examine possible interactions with photoperiod, mice housed in long (16L:8D) or short (8L:16D) photoperiods were fed either ad lib or 70% of their average ad lib intake. Testes were removed at 2, 4, 6, or 8 wk of experimental treatment. Apoptotic activity was determined by in situ TUNEL labeling and assessment of DNA laddering. Significant (P < 0.05) gonadal regression in response to short days was first detected at 8 weeks in mice fed ad lib. Food-restricted, long-day mice also showed significant testicular regression at 8 wk. Combined exposure to short day lengths and food restriction resulted in significant testicular regression at 6 wk (P < 0.05). TUNEL labeling was slightly, though significantly, elevated in germ cells at 2 and 4 wk in long-day food-restricted mice (P < 0.05). TUNEL labeling was also elevated in short-day food-restricted males at these early times but then increased nearly 5-fold at 6 and 8 wk in these mice (P < 0.001). DNA laddering confirmed elevated apoptosis. Overall apoptotic activity negatively correlated with paired testis mass, plasma testosterone, and spermatogenic index measurements in both ad lib and food-restricted males. Few histological markers of necrotic cell death were observed in any group. Taken together, these results suggest that testicular regression in response to limited caloric intake or short days is mediated by apoptosis.

Animals↗

Spontaneous "regression" of enhanced immune function in a photoperiodic rodent Peromyscus maniculatus.

Short days inhibit reproduction and enhance immune function in deer mice (Peromyscus maniculatus). Their reproductive inhibition is sustained by an endogenous timing mechanism: after ca. 20 weeks in short days, reproductive photorefractoriness develops, followed by spontaneous recrudescence of the reproductive system. It is unknown whether analogous seasonal timing mechanisms regulate their immune function or whether enhanced immune function is sustained indefinitely under short days. In order to test this hypothesis, we housed adult male deer mice under long (16 h light day(-1)) or short (8 h light day(-1)) day conditions for 32 weeks or under long day conditions for 20 weeks followed by 12 weeks of short days. Mice under the long day conditions remained photostimulated over the 32 weeks, whereas mice housed under the short day conditions exhibited gonadal regression followed by photorefractoriness and spontaneous recrudescence. Mice transferred to short days at week 20 were reproductively photoregressed at week 32. Total splenocytes, relative splenic mass and mitogen-activated splenocyte proliferation were greater in those mice transferred to short days at week 20 than in those mice housed under either long or short day conditions for 32 consecutive weeks, and immune function in mice exposed to short days for 32 weeks was comparable with that of long day animals. These data suggest that short day enhancement of immune function is not indefinite. With prolonged (< or = 32 weeks) exposure to short days, several measures of immune function exhibit "spontaneous" regression, restoring long day-like immunocompetence. The results suggest that formal similarities and, possibly, common substrates exist among the photoperiodic timekeeping mechanisms that regulate seasonal transitions in reproductive and immune function.

Animals↗

Brevinema andersonii gen. nov., sp. nov., an infectious spirochete isolated from the short-tailed shrew (Blarina brevicauda) and the white-footed mouse (Peromyscus leucopus).

A spirochete which infects short-tailed shrews (Blarina brevicauda) and white-footed mice (Peromyscus leucopus) has been shown previously to be ultrastructurally and serologically distinct from other spirochetes. Two of the original isolates from Connecticut and Minnesota and 16 new isolates obtained from shrews captured in Minnesota were characterized phenotypically and genetically in this study. A comparative analysis of the 16S rRNA sequences of two shrew isolates and one mouse isolate and the 16S rRNA sequences of 16 other spirochetes and Escherichia coli revealed that these organisms exhibited low levels of similarity (range of similarity values, 73.9 to 77.8%; average level of similarity, 74.7%). The shrew and mouse isolates which we examined formed a deeply branching subgroup that was clearly distinct from the other genera of spirochetes examined. These and other results indicated that the new spirochetes represent a unique taxon in the order Spirochaetales. Accordingly, we propose that they should be classified as members of a new genus, Brevinema. The three strains of Brevinema which we examined had 16S rRNA sequences that were nearly identical. We also compared these isolates by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fatty acid and enzyme analyses, restriction endonuclease analysis, and Southern hybridization and found that the levels of genetic and phenotypic homogeneity among the strains were very high. We concluded that the isolates which we examined were members of a single species, for which we propose the name Brevinema andersonii. The type strain of Brevinema andersonii is CT11616 (= ATCC 43811).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Genetic vaccines protect against Sin Nombre hantavirus challenge in the deer mouse (Peromyscus maniculatus).

We used a deer mouse (Peromyscus maniculatus) infection model to test the protective efficacy of genetic vaccine candidates for Sin Nombre (SN) virus that were known to provoke immunological responses in BALB/c mice (Bharadwaj et al., Vaccine 17, 2836-2843, 1999 ). Protective epitopes were localized in each of four overlapping cDNA fragments that encoded portions of the SN virus G1 glycoprotein antigen; the nucleocapsid gene also was protective. The protective efficacy of glycoprotein gene fragments correlated with splenocyte proliferation in the presence of cognate antigen, but none induced neutralizing antibodies. Genetic vaccines against SN virus can protect outbred deer mice from infection even in the absence of a neutralizing antibody response.

Animals↗

Phylogeography of the deer mouse (Peromyscus maniculatus) provides a predictive framework for research on hantaviruses.

Phylogeographical partitioning of Sin Nombre and Monongahela viruses (hantaviruses) may reflect that of their primary rodent host, the deer mouse (Peromyscus maniculatus). Lack of a comprehensive assessment of phylogeographical variation of the host has precluded the possibility of predicting spatial limits of existing strains of these viruses or geographical regions where novel viral strains might emerge. The complete cytochrome b gene was sequenced for 206 deer mice collected from sites throughout North America to provide a foundation for future studies of spatial structure and evolution of this ubiquitous host. Bayesian analyses of these sequences partitioned deer mice into six largely allopatric lineages, some of which may represent unrecognized species. The geographical distributions of these lineages were probably shaped by Quaternary climatic events. Populations of mice were apparently restricted to refugia during glacial advances, where they experienced genetic divergence. Expansion of these populations, following climatic amelioration, brought genetically distinctive forms into contact. Occurrence of parallel changes in virus strains can now be explored in appropriate regions. In New Mexico, for example, near the location where Sin Nombre virus was first discovered, there are three genetically distinctive lineages of deer mice whose geographical ranges need to be delineated precisely. The phylogeography of P. maniculatus provides a framework for interpreting geographical variability, not only in hosts, but also in associated viral variants and disease transmission, and an opportunity to predict the potential geographical distribution of newly emerging viral strains.

Animals↗

Natural selection drives altitudinal divergence at the albumin locus in deer mice, Peromyscus maniculatus.

In populations that are distributed across steep environmental gradients, the potential for local adaptation is largely determined by the spatial scale of fitness variation relative to dispersal distance. Since altitudinal gradients are generally characterized by dramatic ecological transitions over relatively short linear distances, adaptive divergence across such gradients will typically require especially strong selection to counterbalance the homogenizing effect of gene flow. Here we report the results of a study that was designed to test for evidence of adaptive divergence across an altitudinal gradient in a natural population of deer mice, Peromyscus maniculatus. We conducted a multilocus survey of allozyme variation across a steep altitudinal gradient in the southern Rocky Mountains that spanned several distinct biomes, from prairie grassland to alpine tundra. As a control for the effects of altitude, we also surveyed the same loci in mice sampled along a latitudinal transect through the prairie grassland that ran perpendicular to the east-west altitudinal transect. We used a coalescent-based simulation model to identify loci that deviated from neutral expectations, and we then assessed whether locus-specific patterns of variation were nonrandom with respect to altitude. Results indicated that the albumin locus (Alb) reflects a history of diversifying selection across the altitudinal gradient. This conclusion is supported by two main lines of evidence: (1) Alb was characterized by levels of divergence across the altitudinal transect that exceeded neutral expectations in two consecutive years of sampling (in contrast to the spatial pattern of variation across the latitudinal transect), and (2) levels of divergence at the Alb locus exhibited a positive association with altitudinal distance in both years (in contrast to the pattern observed at unlinked loci). We conclude that clinal variation at the Alb locus reflects a balance between gene flow and diversifying selection that results from elevational changes in fitness rankings among alternative genotypes.

Adaptation, Physiological↗

Testosterone and photoperiod interact to affect spatial learning and memory in adult male white-footed mice (Peromyscus leucopus).

Gonadal hormones affect spatial learning and memory in mammals and circulating gonadal hormone concentrations fluctuate by season. Most nontropical rodents are spring/summer breeders and males display higher testosterone concentrations during the breeding season compared with the nonbreeding season (fall/winter). Seasonal patterns of testosterone concentration (as well as many other seasonal modifications of physiology, morphology, and behaviour) are induced by manipulation of photoperiod (day length; i.e. short or long days) in the laboratory. Coincident with reducing testosterone concentration, short days also impair spatial learning and memory performance in male white-footed mice (Peromyscus leucopus) compared with long days. We hypothesized that short-day-induced reduction of testosterone concentrations inhibits spatial learning and memory performance compared with long days. Adult male white-footed mice were maintained in long (16 h light/day) or short (8 h light/day) days for 14 weeks following sham-castration, castration plus saline implant, or castration plus testosterone implant treatment. Spatial learning and memory was assessed using a water maze, and photoperiod-evoked changes in gene expression of sex steroid receptors within the hippocampus were also examined. Castrated, short-day mice with testosterone replacement displayed enhanced water maze performance compared with other short-day mice, but no differences among testosterone treatments were observed in long-day mice. Photoperiod did not affect hippocampal androgen, oestrogen alpha, or oestrogen beta receptor gene expression. These results suggest that photoperiod modulates the effects of testosterone on spatial learning performance by mechanisms indirect of the hippocampus.

Animals↗

Isospora peromysci Davis, 1967 (Apicomplexa: Eimeriidae) in Peromyscus leucopus and P. maniculatus (Rodentia: Cricetidae) from Texas.

Oocysts of Isospora peromysci (Davis, 1967) (Apicomplexa: Eimeriidae) were recovered from the feces of 1/30 (3.3%) white-footed mice, Peromyscus leucopus, in Johnson County, Texas. This report represents a new host and geographic record for the parasite. The coccidium was also found in 1/20 (5.0%) deer mice, P. maniculatus, from the same locale. Morphological data are provided on the sporulated oocyst of I. peromysci and comparisons are made with previously published information on the species from other geographic localities.

Animals↗

Seasonal changes in glycogen level and size of pinealocytes of the white-footed mouse, Peromyscus leucopus: a semiquantitative histochemical study.

Glycogen level in and size of pinealocytes of the feral, white-footed mouse Peromyscus leucopus, were studied by a semiquantitative histochemical method to determine whether seasonal changes exist in them under natural conditions, what temporal pattern they exhibit, and whether 24-hour changes in these parameters exist in different seasons, as shown in the laboratory dd-mice. Marked seasonal changes were seen in both glycogen levels and nuclear densities (ANOVA p less than 0.005). The size of pinealocytes at 09:00 to 10:00 showed one peak (and nadir) seasonal change, with the smallest size in winter (December and February) and a larger size in warmer seasons, with the maximum value in July. Glycogen level in pinealocytes at 09:00 to 10:00 showed bimodal seasonal changes, with lower levels in fall and spring and higher levels in winter and summer. In fall, a circadian trend in glycogen level in pinealocytes was seen, with a higher level at the end of the light period. In winter, the glycogen levels were very high at 09:00, 13:00, 17:00, and 21:00 examined and showed dampening of time-of-day differences. On the other hand, the size of pinealocytes followed a time-of-day change (P less than 0.005), being largest at 13:00 and smallest at 21:00. Thus, marked changes in quantitative structure and chemical activities, suggesting changes in functional activity, in pinealocytes were noted especially in severe, cold winter.

Acclimatization↗

Gonadal regression induced by caloric restriction is not mediated by the pineal gland in deer mice (Peromyscus maniculatus).

The role of the pineal gland in mediating reproductive regression in response to nonphotoperiodic cues was assessed. A proportion of deer mice (Peromyscus maniculatus) undergo gonadal regression subsequent to moderate food restriction. The reproductive regression after inanition qualitatively and quantitatively resembles short-day-induced regression. The physiological mechanisms responsible for gonadal regression after food restriction are unknown. The hypothesis that the mechanisms underlying photoperiodic responsiveness also mediate testicular regression caused by reduced food consumption was tested. Males were pinealectomized or received sham operations. Upon recovery, food availability was restricted to 70% of ad libitum intake. After 8 weeks, the reproductive condition was examined. Pinealectomy did not prevent gonadal regression, suggesting that the pineal gland does not mediate caloric information in this species.

Animals↗

Short photoperiod affects reproductive function but not dehydroepiandrosterone concentrations in male deer mice (Peromyscus maniculatus).

Cessation of breeding is central among the suite of winter-coping strategies used by small rodents to survive energy-demanding winter conditions. Animals use photoperiod to predict the onset of winter and initiate, well in advance of deteriorating conditions, seasonal adaptations. Exposure to short photoperiod leads to regression of the reproductive system in long-day breeding animals. Likewise, exposure to short days leads to enhanced immune function among several rodent species studied. Because dehydroepiandrosterone (DHEA) increases immune function in virtually all studies reported to date, we sought to determine if DHEA concentrations might be influenced by photoperiod, thereby suggesting a mechanism whereby short photoperiod may enhance immune function. Male deer mice (Peromyscus maniculatus) were exposed to either short or long days for 10 weeks. Short photoperiods caused significant reduction in all reproductive organs measured relative to animals housed in long days. However, DHEA concentrations did not differ between short- and long-day mice. Taken together, these data suggest that short-day enhancement of immune function in deer mice is independent of DHEA concentrations.

Adipose Tissue↗

ACTIVITY RHYTHM IN PEROMYSCUS: ITS INFLUENCE ON RATES OF RECOVERY FROM NEMBUTAL.

Injection of sublethal doses of Nembutal (sodium pentobarbital) into deer mice, Peromyscus maniculatus rufinus (Merriam), at diflerent times in their daily activity cycle revealed large differences in rates of recovery. By taking the phase of the circadian rhythm into account, the accuracy obtained in pharmaceutical and physiological bioassays could be increased.

Activity Cycles↗

PEROMYSCUS LEUCOPUS: AN INTERESTING SUBJECT FOR STUDIES OF SOCIALLY INDUCED STRESS RESPONSES.

White-footed mice, Peromyscus leucopus, possess several characteristics which make them interesting subjects for the experimental study of social interactions and stress physiology: tolerance of very high cage densities among social congeners; marked behavioral intolerance among social strangers; exceptionally large adrenal glands; and adrenal and eosinophil responses sensitive to social disturbance.

Adrenal Glands↗

TELEMETRY OF HOMING BEHAVIOR BY THE DEERMOUSE, PEROMYSCUS.

Miniature transmitters (weighing 2.5 to 2.7 grams, including encapsulation) implanted subcutaneously in deermice (Peromyscus) radiate a pulsed signal at 27 megacycles per second which can be detected by a simple antenna at a distance of 45 meters. The radio signal indicates movements of the deermice, periods of activity, and the location of occupied nests. One mouse was traced as it returned to its nest 300 meters in 1 hour. This rate of homing is many times more rapid than the rate usually determined by conventional methods for tracking small terrestrial mammals.

Animals↗

AUTOSOMALLY DETERMINED POLYMORPHISM OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE IN PEROMYSCUS.

Glucose-6-phosphate dehydrogenase commonly occurs in at least two forms in most tissues of the deer mouse, Peromyscus maniculatus, as demonstrated by starch-gel electrophoresis. An autosomally determined genetic polymorphism in one of the enzymes was discovered. A hybrid molecule occurs in the heterozygote; this suggests a dimeric structure of this enzyme.

Animals↗

Genetic diversity of Borrelia burgdorferi sensu stricto in Peromyscus leucopus, the primary reservoir of Lyme disease in a region of endemicity in southern Maryland.

In the north central and northeastern United States, Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme disease (LD), is maintained in an enzootic cycle between the vector, Ixodes scapularis, and the primary reservoir host, Peromyscus leucopus. Genetic diversity of the pathogen based on sequencing of two plasmid-located genes, those for outer surface protein A (ospA) and outer surface protein C (ospC), has been examined in both tick and human specimens at local, regional, and worldwide population scales. Additionally, previous studies have only been conducted with tick or human specimens at the local population level in areas with high LD transmission rates. This study examined the genetic diversity of circulating borreliae in the reservoir population from a large region of the western coastal plains of southern Maryland, where moderate numbers of human LD cases are reported. Six ospA mobility classes, including two that were not previously described, and eight ospC groups were found among the P. leucopus samples. Twenty-five percent of all specimens were infected with more than one ospA or ospC variant. The frequency distribution of variants was homogeneous, both locally and spatially. The spirochete diversity found in Maryland was not as high as that observed among northern tick populations, yet similar genotypes were observed in both populations. These results also show that mice are important for maintaining Borrelia variants, even rare variants, and that reservoir populations should therefore be considered when assessing the diversity of B. burgdorferi.

Animals↗