White-footed Mice Peromyscus Leucopus Research Articles

Apneic uptake of atmospheric O2 by deeply hypothermic nestlings of the white-footed mouse (Peromyscus leucopus): circulation and lungs.

Nestling white-footed mice (Peromyscus leucopus) are born in the earliest days of spring in cold climates. If the nestlings are by accident exposed to ambient temperatures near freezing (0-7°C) at early ages (2-10 days old), they may experience body temperatures (Tbs) equally low. During such hypothermia, although their heart keeps beating, they become apneic (cease inhaling and exhaling). However, they have an exceptional ability (e.g., compared to Mus musculus) to tolerate these conditions for at least several hours, after which they revive if rewarmed by parents. This paper addresses the physiology of the apneic period. We show that apneic, hypothermic nestlings undergo physiologically important exchanges of gases with the atmosphere. These gas exchanges do not occur across the skin. Instead they occur via the trachea and lungs even though the animals are apneic. Most significantly, when hypothermic neonates are in apnea in ordinary air, they take up O2 steadily from the atmosphere throughout the apneic period, and the evidence available indicates that this O2 uptake is essential for the nestlings' survival. At Tbs of 2-7°C, the nestlings' rate of O2 consumption varies quasi-exponentially with Tb and averages 0.04 mL O2 g- 1 h- 1, closely similar to the rate expressed by adult mammalian hibernators in hibernation at similar Tbs. Morphometric analysis indicates that, at all focal ages, O2 transport along the full length of the trachea can take place by diffusion at rates adequate to meet the measured rates of metabolic O2 consumption.

Invasive shrubs differentially alter autumnal activity for three common small-mammal species.

Seasonal variation in animal activity influences fitness and the intensity of ecological interactions (e.g., competition, predation), yet aspects of global change in the Anthropocene may catalyze shifts in seasonal activity. Invasive plants are components of global change and can modify animal daily activity, but their influence on animal seasonal activity is less understood. We examined how invasive woody shrubs (Autumn olive [Elaeagnus umbellata] and Amur honeysuckle [Lonicera maackii]) affect seasonal activity of three common small-mammal species by coupling experimental shrub removal with autumnal camera trapping for two consecutive years at six paired forest sites (total 12 plots). Eastern chipmunks (Tamias striatus) foraged more, and foraging was observed at least 20 days longer, in shrub-invaded forests. White-footed mice (Peromyscus leucopus) foraged more in invaded than cleared plots in one study year, but P. leucopus autumn activity timing did not differ between shrub-removal treatments. Fox squirrel (Sciurus niger) activity displayed year-specific responses to shrub removal suggesting intraannual cues (e.g., temperature) structure S. niger autumnal activity. Our work highlights how plant invasions can have species-specific effects on seasonal animal activity, may modify the timing of physiological processes (e.g., torpor), and could generate variation in animal-mediated interactions such as seed dispersal or granivory.

Characterizing phenotypic data of Peromyscus leucopus compared to C57BL/6J Mus musculus and diversity outbred (DO) Mus musculus

Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.

Patterns of acorn selection in Peromyscus mice and possible implications in a changing climate

Abstract Rodents play a key role in forest regeneration by dispersing seeds and interspecific differences in seed preferences could have important consequences for forest growth. The White-footed Mouse (Peromyscus leucopus) and Deer Mouse (Peromyscus maniculatus gracilis) are 2 closely related species that can exploit Red Oak (Quercus rubra) acorns but may display different preference levels due to the high tannin concentration present in these acorns. Here we investigated how White-footed Mice and Deer Mice differ in their ability to exploit Red Oak acorns. We conducted a cafeteria-style experiment where we offered mice (n = 61) acorns of Red Oak and Bur Oak (Q. macrocarpa; control seed with lower tannin levels) and video-recorded their preference and the acorn fate (consumed or cached). Using mixed-effects models, we found that both mouse species selected and consumed Bur Oak acorns at a high rate; however, White-footed Mice were 6.67 times more likely to select and consume Red Oak acorns than Deer Mice. Furthermore, White-footed Mice tended to cache Red Oak acorns near the surface where there is a higher chance of germination, while they usually consumed Bur Oak acorns. Our results suggest that Red Oaks have a better strategy for avoiding predation than Bur Oaks (i.e., high tannin levels leading to caching), and the strong interaction between the White-footed Mouse and Red Oak might be an important mechanism behind the current range expansion of both species in response to climate change.

Prevalence of Baylisascaris procyonis in wild rodents in central Georgia, USA

Raccoon roundworm, Baylisascaris procyonis, is a zoonotic parasite of raccoons (Procyon lotor) that needs a One Health approach to better inform risks to human and animal health. The few studies on B. procyonis in wild rodents have primarily focused on white-footed mice (Peromyscus leucopus). This study aimed to determine the prevalence and rodent host range of B. procyonis in Georgia (USA) and investigate differences in prevalence at urban/fragmented sites and rural/agriculture sites. We sampled 99 rodents of five species. Larvae were recovered from seven of 78 (9.0%) white-footed mice with a mean of 4.4 larvae (range 1–12). One mouse had a single larva in the brain. Prevalence was not different between urban and rural sites. This report extends the geographic range of this parasite and confirms that rodents serve as paratenic hosts in the southern range. Therefore, baylisascariasis should be considered a differential for neurologic domestic animals, wildlife, or people in this region.

Restored Wetland Size and Age Influence Small Mammal Communities in West Virginia, USA

Small mammals are important, albeit often overlooked, fauna in wetland restoration projects. However, it is essential to evaluate factors that influence small mammal community metrics in restored wetlands to maximize wetland restoration effectiveness. Previous studies found that vegetation differed as restored wetlands aged and that wetland age may play a role in the presence of amphibians and birds. Therefore, we assessed whether wetland age influenced small mammals. We also evaluated 17 environmental factors in restored wetlands that could influence small mammal communities in these wetlands. To assess and evaluate the effects of age and environmental factors on the small mammal community, we appraised 14 restored wetlands in West Virginia, USA, in the summers of 2020 and 2021 for small mammal community metrics, specifically relative abundance, diversity, richness, and evenness. We captured six species of small mammals: deer mice (Peromyscus maniculatus), white-footed mice (Peromyscus leucopus), meadow voles (Microtus pennsylvanicus), meadow jumping mice (Zapus hudsonius), northern short-tailed shrews (Blarina brevicauda), and eastern chipmunks (Tamias striatus). We found that the relative abundance of deer mice, white-footed mice, and meadow voles decreased with wetland age. However, both species diversity and evenness increased with wetland age. Wetland size influenced the relative abundance of white-footed mice, meadow jumping mice, and all small mammals combined. Although the relative abundance of white-footed mice and total small mammals decreased with wetland size, the relative abundance of meadow jumping mice increased with wetland size. Wetland managers should consider wetland age and size when designing wetlands to facilitate small mammal communities.

White-footed mouse (Peromyscus leucopus) response to restoration of grassland alvar

Grassland alvar is a rare plant community that occurs throughout North America and northern Europe, and may require control of encroaching vegetation to be maintained or restored. We evaluated the hypothesis that restoration techniques used to restore the alvar ecosystem do not lead to declines in small mammal abundance. More specifically, we used a Before-After Control-Impact (BACI) design to compare how two methods of vegetation control, prescribed burns and mechanical removal, affected small mammal populations. The restoration was conducted beginning in 2019 on Pelee Island, Ontario, Canada. Live trapping of small mammals and associated vegetation sampling were conducted before and after on treatment and control locations. The only small mammal species to be caught during the study was the white-footed mouse ( Peromyscus leucopus (Rafinesque, 1818)), which had an observed decrease across all treatment sites and the control site. Generalized linear mixed effects models demonstrated that the main effects of treatment and year best explained mouse abundance at the site level. Interannual variability appeared to explain more variation in mouse abundance than treatment effects. Our study did not provide strong evidence that the vegetation control measures we employed might limit white-footed mouse abundance.

Survey of white-footed mice (Peromyscus leucopus) in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses

Diverse mammalian species display susceptibility to SARS-CoV-2. Potential SARS-CoV-2 spillback into rodents is understudied despite their host role for numerous zoonoses and human proximity. We assessed exposure and infection among white-footed mice (Peromyscus leucopus) in Connecticut, USA. We observed 1% (6/540) wild-type neutralizing antibody seroprevalence among 2020–2022 residential mice with no cross-neutralization of variants. We detected no SARS-CoV-2 infections via RT-qPCR, but identified non-SARS-CoV-2 betacoronavirus infections via pan-coronavirus PCR among 1% (5/468) of residential mice. Sequencing revealed two divergent betacoronaviruses, preliminarily named Peromyscus coronavirus-1 and -2. Both belong to the Betacoronavirus 1 species and are ~90% identical to the closest known relative, Porcine hemagglutinating encephalomyelitis virus. In addition, to provide a comparison, we also screened a species with significant SARS-CoV-2 infection and exposure across North America: the white-tailed deer (Odocoileus virginianus). We detected no active coronavirus infections and 7% (4/55) wild-type SARS-CoV-2 neutralizing antibody seroprevalence. Low SARS-CoV-2 seroprevalence suggests white-footed mice may not be sufficiently susceptible or exposed to SARS-CoV-2 to present a long-term human health risk. However, the discovery of divergent, non-SARS-CoV-2 betacoronaviruses expands the diversity of known rodent coronaviruses and further investigation is required to understand their transmission extent.

To what extent do physiological tolerances determine elevational range limits of mammals?

A key question in biology concerns the extent to which distributional range limits of species are determined by intrinsic limits of physiological tolerance. Here, we use common-garden data for wild rodents to assess whether species with higher elevational range limits typically have higher thermogenic capacities in comparison to closely related lowland species. Among South American leaf-eared mice (genus Phyllotis), mean thermogenic performance is higher in species with higher elevational range limits, but there is little among-species variation in the magnitude of plasticity in this trait. In the North American rodent genus Peromyscus, highland deer mice (Peromyscus maniculatus) have greater thermogenic maximal oxygen uptake ( ) than lowland white-footed mice (Peromyscus leucopus) at a level of hypoxia that matches the upper elevational range limit of the former species. In highland deer mice, the enhanced thermogenic in hypoxia is attributable to a combination of evolved and plastic changes in physiological pathways that govern the transport and utilization of O2 and metabolic substrates. Experiments with Peromyscus mice also demonstrate that exposure to hypoxia during different stages of development elicits plastic changes in cardiorespiratory traits that improve thermogenic via distinct physiological mechanisms. Evolved differences in thermogenic capacity provide clues about why some species are able to persist in higher-elevation habitats that lie slightly beyond the tolerable limits of other species. Such differences in environmental tolerance also suggest why some species might be more vulnerable to climate change than others.

It’s about time: small mammal communities and Lyme disease emergence

Theory predicts that biodiversity changes due to climate warming can mediate the rate of disease emergence. The mechanisms linking biodiversity-disease relationships have been described both theoretically and empirically but remain poorly understood. We investigated the relations between host diversity and abundance and Lyme disease risk in southern Quebec, a region where Lyme disease is rapidly emerging. We found that both the abundance of small mammal hosts and the relative abundance of the tick’s natural host, the white-footed mouse (Peromyscus leucopus), influenced measures of disease risk in tick vectors (Borrelia burgdorferi infection abundance and prevalence in tick vectors). Our results suggest that the increase in Lyme disease risk is modulated by regional processes involving the abundance and composition of small mammal assemblages. However, the nature and strength of these relationships was dependent both on time and geographic area. The strong effect of P. leucopus abundance on disease risk we report here is of significant concern, as this competent host is predicted to increase in abundance and occurrence in the region, with the northern shift in the range of North American species under climate warming.

Zoonotic implications of white-footed mice habitat selection and territoriality in fragmented landscapes.

White-footed mouse (Peromyscus leucopus) populations can thrive in fragmented suburban and urban parks and residential spaces and play a pivotal role in the spread and prevalence of tick-borne diseases. We collected spatial data on 58 individual mice living at the intersection of county park land and residential land in suburban Howard County, MD, U.S.A. We analyzed mouse density, home-range size and overlap, and a Bayesian mixed-effects model to identify the habitats where they were found relative to where they were caught, as well as a resource selection function for general habitat use. We found that as mouse density increased, home-range size decreased. The overlap indices and the resource selection function supported territoriality coupled with site-specific space use in these suburban mouse populations. While mice occurred in open areas, forest edge, and forest, they showed a strong preference for forested areas. Interestingly, mice captured only 30 to 40 m into the forest rarely used the nearby private yards or human structures and this has direct implications for the placement of rodent-targeted tick control treatments. Our study supports the need for zoonotic disease management frameworks that are based on site-specific land cover characteristics as well as specific management objectives.

Efficacy of a federally approved flea bait, orally administered to white-footed mice (Peromyscus leucopus), against blood feeding Ixodes scapularis larvae under simulated field conditions.

A promising alternative approach to conventional vector control practices is the use of systemic insecticides/acaricides orally administered to relevant mammalian host species to control blood feeding disease vectors. In the United States, Lyme disease continues to be the most prevalent vector-borne disease with the Centers for Disease Control and Prevention estimating approximately 500,000 Lyme disease infections each year. Previous research has demonstrated the potential usefulness of a low dose fipronil bait in controlling Ixodes scapularis larvae feeding on white-footed mice. However, no such acaricide-only product is approved for use in treating white-footed mice to control I. scapularis. The purpose of the study was to evaluate the use of a federally approved fipronil flea control bait (Grain Bait) in controlling I. scapularis parasitizing white-footed mice (Peromyscus leucopus). A simulated field trial was conducted in which Grain Bait was presented to grouped white-footed mice alongside an alternative diet for 168h. Mice were fitted with capsules and manually parasitized with I. scapularis larvae. Replete larvae detaching from each mouse were collected and monitored for molting to nymphs. The inside of each capsule was observed to evaluate tick attachment. Blood was collected from all Treatment group mice via cardiac puncture to determine the fipronil sulfone concentration in plasma (CP) for each animal. Results indicated that Grain Bait would be consumed in the presence of an alternative diet and that bait acceptance was greater for males, relative to females. Treatment with Grain Bait prevented 100% larvae from feeding to repletion at Day 7 post-exposure and prevented 80% of larvae from feeding to repletion and 84% from molting at Day 21 post-exposure, relative to Control groups. Molted nymphs were not recovered from mice that had CP detectable ≥18.4ng/ml. The results suggest that this federally approved flea product could be utilized for tick control and that other medically important vector-host relationships should be considered.

Orally delivered fipronil-laced bait reduces juvenile blacklegged tick (Ixodes scapularis) burdens on wild white-footed mice (Peromyscus leucopus)

While the topical acaricidal treatment of rodent pathogen reservoirs has been readily explored over the past several decades, oral systemic acaricidal treatment is only recently gaining traction as an alternative approach to the management of ticks and tick-borne pathogens. Recent laboratory tests have shown promise in the effectiveness of this systemic strategy against the blacklegged tick (Ixodes scapularis) and a Canadian field evaluation was recently published, but no recent field data from the United States yet exist. With this research, we sought to field deploy a commercially available fipronil-laced bait (Kaput® Flea Control Bait, Scimetrics LLC., Wellington, CO, USA; 0.005% fipronil; Environmental Protection Agency Reg. No. 72500-28), in an alternate use targeting white-footed mice (Peromyscus leucopus) to determine bait acceptance and potential impacts to juvenile I. scapularis burdens. Bait was readily accepted by wild P. leucopus and other rodent reservoirs. An ad libitum distribution strategy as well as placing smaller volumes of fipronil-laced bait within individual Sherman traps both resulted in significant reductions (57-94%) in juvenile I. scapularis burdens as compared to control over two years. The oral delivery of systemic acaricides shows promise in reduction of I. scapularis burdens on P. leucopus and should be further explored to determine effectiveness on host-seeking tick abundances, associated pathogen infection, and potentially incorporated into integrated tick management programs.

Detection of Ehrlichia muris eauclairensis in Blacklegged Ticks (Ixodes scapularis) and White-Footed Mice (Peromyscus leucopus) in Massachusetts.

In 2011, Ehrlichia muris eauclairensis (EME) was described as a human pathogen spread by the blacklegged tick, Ixodes scapularis. Until very recently, its reported distribution was limited to the upper midwestern United States, mainly in Minnesota and Wisconsin. In this study, we report the detection of EME DNA in 4 of 16,146 human biting I. scapularis ticks submitted from Massachusetts to a passive tick surveillance program. Active tick surveillance yielded evidence of EME local transmission in the northeastern United States through detection of EME DNA in 2 of 461 host-seeking I. scapularis nymphs, and in 2 white-footed mice (Peromyscus leucopus) of 491 rodent samples collected in the National Ecological Observatory Network (NEON) Harvard Forest site in Massachusetts.

Of mice, ticks, and fleas: host behaviour and co-occurring parasites

Host behaviour should be a key determinant of the acquisition of “sit-and-wait” and nidicolous ectoparasitic arthropods that ambush the host in their environment and/or nest. Here, we tested the association between parasitism and individual differences in exploratory and grooming behaviours in white-footed mice ( Peromyscus leucopus (Rafinesque, 1818)), the primary host for the black-legged tick ( Ixodes scapularis Say, 1821) in its larval stage. During 4333 captures of 1035 individual mice over five summers (2016–2020) in Ontario, Canada, the probability and intensity of tick parasitism were both significantly higher when the mouse was also parasitized by fleas, suggesting co-occurrence of these two parasites on host mice. Distance moved by mice in a novel environment was negatively and positively affected by tick and flea parasitism, respectively. Interestingly, there was a significant “tick × flea” statistical interaction on distance moved, such that fleas were positively associated with activity/exploration only when ticks were absent. There was no relationship between grooming behaviour and parasite presence. This study suggests that co-occurring parasite species (ticks and fleas) may differentially affect their host's behaviour depending on the presence/absence of the other parasite on the host. Alternatively, host behaviour may differentially affect individual susceptibility to being infested with ticks, fleas, or both.

Patterns of Genetic And Epigenetic Diversity Across A Range Expansion in The White-Footed Mouse (Peromyscus Leucopus).

Populations at the leading front of a range expansion must rapidly adapt to novel conditions. Increased epigenetic diversity has been hypothesized to facilitate adaptation and population persistence via non-genetic phenotypic variation, especially if there is reduced genetic diversity when populations expand (i.e., epigenetic diversity compensates for low genetic diversity). In this study, we use the spatial distribution of genetic and epigenetic diversity to test this hypothesis in populations of the white-footed mouse (Peromyscus leucopus) sampled across a purported recent range expansion gradient. We found mixed support for the epigenetic compensation hypothesis and a lack of support for expectations for expansion populations of mice at the range edge, which likely reflects a complex history of expansion in white-footed mice in the Upper Peninsula of Michigan. Specifically, epigenetic diversity was not increased in the population at the purported edge of the range expansion in comparison to the other expansion populations. However, input from an additional ancestral source populations may have increased genetic diversity at this range edge population, counteracting the expected genetic consequences of expansion, as well as reducing the benefit of increased epigenetic diversity at the range edge. Future work will expand the focal populations to include expansion areas with a single founding lineage to test for the robustness of a general trend that supports the hypothesized compensation of reduced genetic diversity by epigenetic variation observed in the expansion population that was founded from a single historical source.

Individual variation in heat substitution: is activity in the cold energetically cheaper for some individuals than others?

In many endotherms, a potentially important yet often overlooked mechanism to save energy is the use of the heat generated by active skeletal muscles to replace heat that would have been generated by thermogenesis (i.e. 'activity-thermoregulatory heat substitution'). While substitution has been documented numerous times, the extent of individual variation in substitution has never been quantified. Here, we used a home-cage respirometry system to repeatedly measure substitution through the concomitant monitoring of metabolic rate (MR) and locomotor activity in 46 female white-footed mice (Peromyscus leucopus). A total of 117 measures of substitution were taken by quantifying the difference in the slope of the relationship between MR and locomotor activity speed at two different ambient temperatures. Consistency repeatability (±s.e.) of substitution was 0.313 (±0.131); hence, about a third of the variation in substitution occurs at the among-individual level. Body length and heart mass were positively correlated with substitution whereas surface area was negatively correlated with substitution. These three sub-organismal traits accounted for the majority of the among-individual variation (i.e. individual differences in substitution were not significant after accounting for these traits). Overall, our results imply that the energetic cost of activity below the thermoneutral zone is consistently cheaper from some individuals than others, and that the energy saved from substitution might be available to invest in fitness-enhancing activities.

Reproductive and developmental toxicity of perfluorooctane sulfonate (PFOS) in the white-footed mouse (Peromyscus leucopus)

Concerns about per- and polyfluoroalkyl substances (PFAS) stem from their ubiquitous presence in the environment, bioaccumulation, resistance to degradation, and toxicity. Previously, toxicity data relevant to ecological risk assessment has largely been aquatic, terrestrial invertebrates, or avian in origin. In this study, repeated oral exposures of perfluorooctane sulfonate (PFOS) were administered to white-footed mice (Peromyscus leucopus) to evaluate effects on reproduction and development. Prenatal exposure to high doses of PFOS caused neonatal mortality, though growth and development were unaffected by low doses. Additionally, parental (P) generation animals exhibited increased liver:body weight, increased hepatocyte cytoplasmic vacuolization, and decreased serum thyroxine (T4) levels. Total litter loss was selected as the protective critical effect in this study resulting in a benchmark dose low (BMDL) of 0.12 mg/kg-d PFOS. Importantly, PFOS exposure has been linked to reduced adult recruitment in myriad species and at similar thresholds to this study. Similarities in critical/toxicologic effects across taxa may add confidence in risk assessments at sites with multiple taxa or environments.

Multi-scale analysis of habitat fragmentation on small-mammal abundance and tick-borne pathogen infection prevalence in Essex County, MA.

Habitat fragmentation and heterogeneity transform otherwise contiguous tracks of forest into smaller patches in the northeastern U.S. and likely impact abundances, movement patterns, and disease transmission pathways for small-mammal communities at multiple scales. We sought to determine the structure of a small-mammal community in terms of mammal abundance and infection prevalence of Borrelia burgdorferi sensu stricto (s.s.), Anaplasma phagocytophilum, and Babesia microti within a fragmented landscape in Essex County, Massachusetts, USA. We studied communities at multiple spatial scales, including vegetation, edge type, and landscape (including 200-m, 500-m, and 1000-m radii) scales. A total of 16 study sites were chosen to represent four edge types: interior forest, pasture edge, natural edge, and residential edge. At each site, we trapped small mammals and conducted vegetation surveys and GIS analysis. Upon capture, a tissue sample was collected to analyze for presence of pathogens. Northern short-tailed shrew (Blarina brevicauda) abundance did not differ based on edge type, whereas abundance of the white-footed mouse (Peromyscus leucopus) was greatest at pasture edges, although the relationship was relatively weak. White-footed mouse abundance was negatively associated with amount of forested area within a 500-m radius, whereas northern short-tailed shrew abundance demonstrated a positive relationship with fragmentation indices at the 200-m radius. White-footed mice captured at interior-forest habitat were more likely be infected with B. burgdorferi (s.s.) than individuals from edge habitat. Greater prevalence of B. burgdorferi infection of white-footed mice in forest interiors compared to edge habitats counters previous studies. Reasons for this and implications are discussed.

Postglacial colonization in the Great Lakes Region by the white-footed mouse (Peromyscus leucopus): conflicts between genomic and field data

Abstract For regions that were covered by ice during the Pleistocene glaciations, species must have emigrated from unglaciated regions. However, it can be difficult to discern when and from what ancestral source populations such expansions took place, especially since warming climates introduce the possibility of very recent expansions. For example, in the Great Lakes region, pronounced climatic change includes past glaciations as well as recent, rapid warming. Here we evaluate different expansion hypotheses with a genomic study of the white-footed mouse (Peromyscus leucopus noveboracensis), which is one of the most common mammals throughout the Great Lakes region. Ecological surveys coupled with historical museum records suggest a recent range expansion of P. leucopus associated with the warming climate over the last decades. These detailed records have yet to be complemented by genomic data that provide the requisite resolution for detecting recent expansion, although some mitochondrial DNA (mtDNA) sequences have suggested possible hypotheses about the geography of expansion. With more than 7,000 loci generated using RADseq, we evaluate support for multiple hypotheses of a geographic expansion in the Upper Peninsula of Michigan (UP). Analysis of a single random single-nucleotide polymorphism per locus revealed a fine-scale population structure separating the Lower Peninsula (LP) population from all other populations in the UP. We also detected a genetic structure that reflects an evolutionary history of postglacial colonization from two different origins into the UP, one coming from the LP and one coming from the west. Instead of supporting a climate-driven range expansion, as suggested by field surveys, our results support more ancient postglacial colonization of the UP from two different ancestral sources. With these results, we offer new insights about P. leucopus geographic expansion history, as well as a more general phylogeographic framework for testing range shifts in the Great Lakes region.