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PubMed2001

MHC class II beta sequence diversity in the deer mouse (Peromyscus maniculatus): implications for models of balancing selection.

We studied population polymorphism at a major histocompatibility complex (MHC) class II beta gene in the deer mouse (Peromyscus maniculatus). We found that: (i) a single population of P. maniculatus has significantly higher levels of DNA and protein sequence diversity than worldwide samples from homologous genes in other taxa, including humans and mice; and (ii) the genealogy of allelic sequences in P. maniculatus deviates significantly from theoretical expectation under a model of symmetric balancing selection, in that alleles are relatively more divergent than expected. We suggest that the observation of high levels of pairwise allelic sequence divergence and deviation of the genealogy from theoretical expectation in P. maniculatus together provide support for a divergent allele advantage model for the maintenance of MHC polymorphism.

Alleles↗
PubMed2002

Characterization of Peromyscus MHC class II beta sequences by ligation-anchored RT-PCR and denaturing gradient gel electrophoresis.

We characterized MHC class II beta sequences in deermice (genus Peromyscus), which are amongst the most common mammals in North America. We find evidence for two different families of class II beta loci, most closely related to either the A-type or E-type loci in Mus. Population studies suggest the presence of more than one A-type locus but only one E-type locus for the species investigated.

Amino Acid Sequence↗
PubMed2001

Genetic (RAPD) diversity in Peromyscus maniculatus populations in a naturally fragmented landscape.

We assessed the effects of long-term habitat fragmentation on genetic (random amplified polymorphic DNA) diversity in 11 Peromyscus maniculatus populations in the Lake Superior watershed. We analysed genetic structure at two spatial scales and the effect of island size and isolation on genetic diversity. At the regional scale, island populations differed from mainland populations (FST = 0.36), but mainland populations did not differ from each other (FST = 0.01). At the local scale, populations of the main island of Isle Royale differed from adjacent islet populations (P < 0.001; Monte Carlo approximation of Fisher's exact test), but not from each other (combined P = 0.63). Although geographical distance and genetic distance were positively correlated (P < 0.01; Mantel test), cluster analysis revealed some inconsistencies. Finally, genetic diversity was inversely related to isolation (P = 0.01), but had an unexpectedly negative relationship with island area (P = 0.03). The genetic structure of P. maniculatus populations in portions of the Lake Superior watershed appears to have been affected by long-term habitat fragmentation.

Animals↗
PubMed2003

Historical demography and genetic structure of sister species: deermice (Peromyscus) in the North American temperate rain forest.

To investigate the evolutionary and biogeographical history of Peromyscus keeni and P. maniculatus within the coastal forest ecosystem of the Pacific Northwest of North America, we sampled 128 individuals from 43 localities from southeastern Alaska through Oregon. We analysed mitochondrial DNA variation using DNA sequence data from the mitochondrial cytochrome-b (cyt-b) gene and control region, and we found two distinct clades consistent with the morphological designation of the two species. The sequence divergence between the two clades was 0.0484 substitutions per site for cyt-b and 0.0396 for the control region, suggesting that divergence of the two clades occurred during the middle to late Pleistocene. We also examined the historical demography of the two clades using stepwise and exponential expansion models, both of which indicated recent rapid population growth. Furthermore, using the program migrate we found evidence of migration from populations north of the Fraser River (British Columbia) to the south in both clades. This study demonstrates the utility of these model-based demographic methods in illuminating the evolutionary and biogegographic history of natural systems.

Animals↗
PubMed2002

The effects of inbreeding on testicular sperm concentration in Peromyscus polionotus.

Inbreeding effects on fitness have most often been quantified via juvenile mortality. However, inbred adults may suffer from inbreeding depression if their fertility or fecundity is compromised as a consequence of inbreeding. Here, the effects of inbreeding on male fertility in oldfield mice, Peromyscus polionotus, were examined. Testicular sperm concentration was assessed in 93 males, 68 of which were paired for breeding. Forty of the 68 paired males failed to produce offspring. Total testicular sperm count, sperm count (g testis)(-1), and testis mass all declined significantly with increasing inbreeding coefficient. Sperm concentration did not significantly impact reproductive success. Although sperm concentration in males of most species can decline to low levels before reproductive impairment is detectable, the declines in testicular sperm concentration found here suggest that inbreeding can affect fertility in adult males. Furthermore, monitoring testicular sperm concentration could provide a mechanism to monitor potential declines in reproductive performance before population-level reproductive success is irreparably impaired. The implications for the management of small, captive and wild populations may be substantial.

Animals↗
PubMed2000

Experimental infection model for Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus).

The relationship between hantaviruses and their reservoir hosts is not well understood. We successfully passaged a mouse-adapted strain of Sin Nombre virus from deer mice (Peromyscus maniculatus) by i.m. inoculation of 4- to 6-wk-old deer mouse pups. After inoculation with 5 ID(50), antibodies to the nucleocapsid (N) antigen first became detectable at 14 d whereas neutralizing antibodies were detectable by 7 d. Viral N antigen first began to appear in heart, lung, liver, spleen, and/or kidney by 7 d, whereas viral RNA was present in those tissues as well as in thymus, salivary gland, intestine, white fat, and brown fat. By 14 d nearly all tissues examined displayed both viral RNA and N antigen. We noted no consistent histopathologic changes associated with infection, even when RNA load was high. Viral RNA titers peaked on 21 d in most tissues, then began to decline by 28 d. Infection persisted for at least 90 d. The RNA titers were highest in heart, lung, and brown fat. Deer mice can be experimentally infected with Sin Nombre virus, which now allows provocative examination of the virus-host relationship. The prominent involvement of heart, lung, and brown fat suggests that these sites may be important tissues for early virus replication or for maintenance of the virus in nature.

Animals↗
PubMed2002

Effects of in utero and lactational ammonium perchlorate exposure on thyroid gland histology and thyroid and sex hormones in developing deer mice (peromyscus maniculatus) through postnatal day 21.

Thyroid gland hormone levels and histology and sex hormone levels in developing deer mice (Peromyscus maniculatus) were measured following in utero and lactational exposure to ammonium perchlorate (AP), a component of rocket fuel and a thyroid toxicant. Breeding pairs were dosed continuously with 0, 1 nM, 1 micro M, or 1 mM concentrations of AP in drinking water from the time of cohabitation until pups from the third litter were weaned. Pups from the second litter were used for evaluation in this study. The active (colloid-containing) thyroid follicle number per unit area was significantly different between treatment groups. The 1-nM and 1-mM treatment groups had significantly fewer active follicles per unit area than did controls. The 1-mM treatment group also had significantly fewer active follicles than the 1- micro M and the 1-nM treatment groups. Total T(4) concentrations were significantly increased in the 1-nM and 1- micro M groups compared to the controls. No significant difference was observed in total T(3) concentrations. None of the 1-mM plasma had concentrations of total testosterone above the detection limit, and only one of the 1- micro M samples was above the detection limit of the assay. All estradiol concentrations were below the detection limits of the assay. In contrast to the situation in adult rodents, it appears that AP increases thyroid hormone production in developing deer mice and produces variable effects with increasing concentrations.

Aging↗
PubMed1980

Aging and ovarian function in the white-footed mouse (Peromyscus leucopus) with specific reference to the development of preovulatory follicles.

A study was made of the effects of increasing age on uterine histology, follicular development and steroidogenesis within the ovary of the white-footed mouse (Peromyscus leucopus). The animals were autopsied on each day of the estrous cycle and ranged from 14 to 49 mos. of age. The data indicated that the animals maintained estrous cycles throughout their lifespan as judged by cyclic changes in uterine histology. In addition these studies showed that aging (1) did not alter ovarian concentrations of testosterone, 17 beta-estradiol or progesterone, (2) resulted in a decrease in the number of primary and preantral follicles during metestrus, proestrus and estrus, (3) increased the percentage of atretic preantral follicles during metestrus only, and (4) did not reduce the number of antral (preovulatory) follicles that develop by proestrus. These observations suggest that in P. leucopus the "rescue" of preantral follicles constitutes the mechanism which compensates for the decrease in the number of smaller follicles and allows the normal number of preovulatory follicles to develop and ovulate. It is also possible that this mechanism exists in the laboratory mouse and rat since species-specific numbers of preovulatory follicles develop in aged cycling animals despite an age-related decrease in the total follicular populations.

Aging↗
PubMed1980

Effects of advancing age on the hypothalamic-pituitary-ovarian axis of the female white-footed mouse (Peromyscus leucopus).

Peromyscus leucopus, with an average lifespan of 48 months, showed unchanged levels of serum luteinizing hormone (LH), estradiol, progesterone, and pituitary LH and prolactin, between the ages of 12 and 48 months. Hypothalamic LH-releasing hormone (LHRH), norepinephrine and dopamine also remained unchanged with advancing age. Ovarian and uterine weight decreased with age, although the changes in uterine weight were not statistically significant. These data indicate that the hypothalamic-pituitary-ovarian axis remains intact with increasing age, accounting for the maintenance of fertility in these animals. The lack of significant changes in these parameters is in very marked contrast to those in the aging laboratory mouse and rat, which show derangements in their reproductive systems midway through their lifespans.

Aging↗
PubMedDate not supplied

Morphological and physiological responses to altitude in deer mice Peromyscus maniculatus.

Individuals within a species, living across a wide range of habitats, often display a great deal of phenotypic plasticity for organ mass and function. We investigated the extent to which changes in organ mass are variable, corresponding to environmental demand, across an altitudinal gradient. Are there changes in the mass of oxygen delivery organs (heart and lungs) and other central processing organs (gut, liver, kidney) associated with an increased sustainable metabolic rate that results from decreased ambient temperatures and decreased oxygen availability along an altitudinal gradient? We measured food intake, resting metabolic rate (RMR), and organ mass in captive deer mice (Peromyscus maniculatus bairdii) at three sites from 1,200 to 3,800 m above sea level to determine whether energy demand was correlated with organ mass. We found that food intake, gut mass, and cardiopulmonary organ mass increased in mice living at high altitudes. RMR was not correlated with organ mass differences along the altitudinal gradient. While the conditions in this study were by no means extreme, these results show that mice living at high altitudes have higher levels of energy demand and possess larger cardiopulmonary and digestive organs than mice living at lower altitudes.

Adaptation, Physiological↗
PubMedDate not supplied

Responses to lactation and cold exposure by deer mice (Peromyscus maniculatus).

Recently, much interest has been expressed in understanding how animals use phenotypic plasticity of tissue size and function to meet increased metabolic demands. We set out to learn (i) whether female deer mice (Peromyscus maniculatus) given lactation (two to seven pups per litter), cold (5 degrees C), or cold plus lactation as energy demands display phenotypic plasticity in organ size and function; (ii) whether that plasticity is similar to laboratory mice given the same demands; and (iii) whether lactational performance in deer mice is derived from limits on central or peripheral organs. We found that deer mice responded to lactation by increasing digestible food intake and increasing the masses of the stomach, small intestine, cecum and liver, and the length of the small intestine. Heart mass was lower in lactating than in nonlactating mice. Cold exposure also caused increases in digestible food intake and increases in the masses of the small intestine, kidney, and heart. We conclude that deer mice display organ tissue plasticity in response to both lactation and cold exposure in a similar manner to laboratory mice. We also conclude that deer mice are not limited by central processing organs because they are able to increase digestive organ size continuously with increased energetic demands.

Adaptation, Physiological↗
PubMedDate not supplied

Immune response, not immune maintenance, is energetically costly in wild white-footed mice (Peromyscus leucopus).

Understanding the cost of immune function is essential for more accurate characterization of energy budgets of animals and better understanding of the role of immunity in the evolution of life-history strategies. We examined the energetic cost of maintaining a normally functioning immune system and mounting a mild immune response in wild male white-footed mice (Peromyscus leucopus). To evaluate the cost of maintaining immunocompetence, we compared resting and daily metabolic rates (RMR; DMR) and masses of body organs of mice whose immune systems were suppressed by cyclophosphamide with those of control mice. To evaluate the cost of mounting an immune response, we measured RMR, DMR, and organ masses in mice whose humoral and cell-mediated immune responses had been stimulated by injections of sheep red blood cells and phytohemagglutinin, respectively. Immunosuppression resulted in a significant reduction in circulating leukocytes, by 225%, but no significant effect on metabolic rates or organ masses. Immunochallenged animals showed no significant differences in metabolic rates compared with control animals but did exhibit significantly smaller dry masses of the small intestine and testes, by 74% and 22%, respectively. We concluded that the cost of maintaining the immune system was minimal. In contrast, there was a significant energetic cost of mounting an immune response that, depending on its magnitude, can be met through reductions in energy allocation to other physiological systems.

Animals↗
PubMed2004

Borrelia burgdorferi infection in a natural population of Peromyscus Leucopus mice: a longitudinal study in an area where Lyme Borreliosis is highly endemic.

Blood samples from Peromyscus leucopus mice captured at an enzootic site in Connecticut were examined for antibodies to and DNA of Borrelia burgdorferi, to characterize the dynamics of infection in this reservoir population. From trappings conducted over the course of 2 transmission seasons, 598 (75%) of 801 serum samples from 514 mice were found to be positive by enzyme immunoassay. Seropositivity correlated with date of capture and mouse age, was similar among locations within the site, increased from 57% to 93% over the course of the transmission season, and was associated with antibodies to outer surface protein (Osp) C, but not to OspA. Longitudinal samples from 184 mice revealed an incidence of 0.2 cases/mouse/week. Nineteen (10%) of 187 samples were found by polymerase chain reaction to be positive for B. burgdorferi, and, of those, 14 (74%) were found to be seropositive. Nearly the entire population of P. leucopus mice became infected with B. burgdorferi by late August, coinciding with the peak activity period of host-seeking larvae uninfected with the spirochete Ixodes scapularis, thereby perpetuating the agent through succeeding generations of ticks.

Animals↗
PubMed1998

Cosegregation of a novel Bartonella species with Borrelia burgdorferi and Babesia microti in Peromyscus leucopus.

During surveillance for various tickborne pathogens in the upper Midwest during the summer and early fall of 1995, a Bartonella-like agent was detected in the blood of mice that were concurrently infected with Borrelia burgdorferi or Babesia microti (or both). The organism was isolated in pure culture after inoculation of blood from wild-caught mice into C.B-17 scid/scid mice. Phylogenetic analysis of the 16S rRNA and the citrate synthase genes showed that the novel Bartonella species and a Bartonella isolate from a mouse captured on Martha's Vineyard, Massachusetts, were closely related to each other and secondarily related to Bartonella grahamii and Bartonella vinsonii. Further analysis of Peromyscus leucopus blood and tissue samples demonstrated that the novel Bartonella species was exclusively found in conjunction with B. burgdorferi and B. microti. Patent coinfection with these agents may be relatively frequent in naturally infected mice.

Animals↗
PubMedDate not supplied

Glycolytic enzyme binding during entrance to daily torpor in deer mice (Peromyscus maniculatus).

Associations of glycolytic enzymes with the subcellular particulate fraction of skeletal muscle and heart were examined during entrance to daily torpor in deer mice (Peromyscus maniculatus). In skeletal muscle a significant decrease in enzyme binding occurred during torpor entrance for phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase, with an additional significant decrease for phosphofructokinase and pyruvate kinase during the deepest state of torpor. Reductions in enzyme binding during torpor entrance also occurred in heart; significant changes were observed in hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase binding. Contrary to the finding of additional reductions in enzyme binding seen in skeletal muscle, significant increases in enzyme binding during the deepest torpor state were observed for hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and lactate dehydrogenase in heart. These results suggest that a decrease in the binding of glycolytic enzymes to subcellular structures in skeletal muscle and heart may be at least partially responsible for initiating the reduction in metabolic rate during torpor entrance. This decreased binding may continue to mediate the metabolic reduction in skeletal muscle throughout torpor; heart, however, may require the use of different molecular mechanisms. The increased binding in heart during the deepest state of torpor may represent an anticipatory response in preparation for increased activity during arousal.

Analysis of Variance↗
PubMed2001

OspA immunization decreases transmission of Borrelia burgdorferi spirochetes from infected Peromyscus leucopus mice to larval Ixodes scapularis ticks.

Recombinant outer surface protein A (OspA) vaccination of wild animal reservoirs has potential application for reducing Borrelia burgdorferi transmission in nature and subsequent risk of human infection. As a major reservoir host, the white-footed mouse (Peromyscus leucopus) is a candidate for a vaccination program designed to reduce infection prevalence in vector ticks. In this study we characterized the effect of various levels of immunization with recombinant OspA-glutathione transferase fusion protein on transmission dynamics from infected P. leucopus to larval ticks. Control mice were vaccinated with glutathione transferase alone. All mice were experimentally infected with B. burgdorferi before vaccination. The immune responses of the immunized mice were assessed by enzyme-linked immunosorbent assay for antibodies to OspA. Transmission of B. burgdorferi from infected mice was determined by xenodiagnosis with uninfected larval ticks. Spirochetes in ticks were counted by direct immunofluorescence assay. The concentration of antibody to OspA increased with each OspA vaccination but most markedly after the first and second vaccinations. In comparison with control mice, there was reduced transmission by OspA-vaccinated mice to uninfected ticks. One, two, or three doses of OspA reduced infection prevalence in xenodiagnostic ticks by 48%, 92%, or 99% and the numbers of spirochetes per tick by 84%, 98%, or 99%, respectively. This study suggests that vaccination of P. leucopus with OspA could reduce transmission to the tick vector in nature despite prior infection of the reservoir host.

Animals↗
PubMed2004

Genetic relatedness of deer mice (Peromyscus maniculatus) infected with Sin Nombre virus.

The deer mouse (Peromyscus maniculatus) is the primary rodent host of Sin Nombre virus (SNV), the principal etiologic agent of hantavirus pulmonary syndrome in the United States. Many characteristics of SNV infections of deer mice are unknown. To better understand the transmission mechanisms of SNV in deer mice, we conducted mark-recapture sampling and genetic analyses to study deer mouse population density and genetic relatedness from 2001 to 2002. We genotyped each deer mouse at 10 microsatellite loci to estimate relatedness among SNV-infected and SNV-uninfected groups, demographic categories, and individuals. Estimates of average overall population densities ranged from 1.15 to 14.95 deer mice/ha. Estimates of average population densities of SNV-infected deer mice ranged from 0 to 1.55 deer mice/ha. When evaluated as groups at one of two study sites, SNV-infected deer mice were more related to one another, on average, than they were to their uninfected cohorts. Pairwise coefficients of relatedness among individuals indicated that several deer mice infected with SNV were closely related. Most infected mice were males. These results are consistent with the hypothesis that transmission of SNV often is associated with breeding activities and aggression among males during the breeding season and suggest that post-birth behavioral associations among adults and juveniles may be a factor in the transmission of SNV.

Animals↗
PubMed1998

Transgenic mice expressing a truncated Peromyscus leucopus TNF-alpha gene manifest an arthritis resembling ankylosing spondylitis.

Several studies have implicated tumor necrosis factor-alpha (TNF-alpha) in autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the role of TNF-alpha in inflammatory arthritis, we generated transgenic mice harboring a truncated Peromyscus leucopus TNF-alpha (Pe-TNF) gene. An arthritic phenotype closely resembling human ankylosing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic phenotype in detail by radiographic and histologic techniques. It consisted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus TNF-alpha gene, in contrast to the RA-like phenotype described in transgenic mice expressing a truncated human TNF-alpha gene. The Pe-TNF transgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-alpha may initiate an autoimmune arthritis resembling ankylosing spondylitis.

Animals↗