Mus (genus)

Mus is a genus of small rodents belonging to the family Muridae and subfamily Murinae, encompassing approximately 39 extant species that are primarily distributed across the Old World, including Eurasia and Africa.^[1] These species are characterized by their compact size, typically ranging from 2 to 30 grams, with features such as prominent eyes, rounded ears, pointed snouts, and long tails often equal to or exceeding head-body length.^[1] The genus is divided into four subgenera—Mus, Pyromys, Coelomys, and Nannomys—each adapted to specific regions: the subgenus Mus (with about 15 species) spans Eurasia and includes the house mouse (Mus musculus), while Pyromys (five species) and Coelomys (four species) are restricted to southeastern Asia and the Indian subcontinent, and Nannomys (African pygmy mice, around 18 species) is endemic to sub-Saharan Africa.^[2] The ecology of Mus species varies widely, from commensal associations with human settlements—particularly in the case of the house mouse, which has achieved a near-cosmopolitan distribution through human-mediated dispersal—to wild habitats such as grasslands, forests, and arid zones across elevations from sea level to over 4,000 meters.^[3][4] These rodents are predominantly nocturnal burrowers, omnivorous feeders on seeds, insects, and vegetation, and exhibit high reproductive rates, with litters of 3 to 12 offspring produced multiple times per year.^[1] While many species remain regionally confined, M. musculus stands out as a significant invasive species and a key model organism in biomedical research due to its genetic tractability and physiological similarities to humans.^[5] Phylogenetically, Mus forms a monophyletic clade within Murinae, with evolutionary divergences estimated from the late Miocene, reflecting adaptations to diverse ecological niches across continents.^[6] Ongoing taxonomic revisions, including recent descriptions of new species in isolated habitats like Ethiopian forests (2022) and Cyprus (2025), underscore the genus's biodiversity and the challenges in delineating species boundaries amid hybridization barriers.^[7][8]

Taxonomy and Classification

Phylogenetic Position

The genus Mus was established by Carl Linnaeus in his Systema Naturae (10th edition), with Mus musculus designated as the type species. This foundational taxonomic work placed Mus within the broader framework of rodents, recognizing its distinct characteristics among small mammals. Mus belongs to the family Muridae, the subfamily Murinae, and the tribe Murini, where it stands as the sole genus.^[9] This placement reflects its position within the diverse Old World rats and mice, emphasizing the tribe's monotypic nature based on molecular and morphological analyses that separate Mus from closely related lineages like Praomyini. The genus encompasses subgenera such as Mus and Nannomys, highlighting internal diversity within this tribal context. The temporal range of Mus extends from the Late Miocene, approximately 10 million years ago, to the present day.^[9] This span underscores the genus's evolutionary persistence amid significant climatic and ecological shifts in Afro-Eurasia. Key diagnostic traits of Mus include its generally smaller body size compared to related genera like Rattus, along with specific dental morphology featuring low-crowned molars with cusps arranged in transverse rows, adapted for a omnivorous diet.^[10] These features, including a dental formula of I 1/1, C 0/0, P 0/0, M 3/3, distinguish Mus from larger, more robust murids with complex lophs on their molars.

Subgenera, Species, and Subspecies

The genus Mus is divided into four monophyletic subgenera: Mus (Palearctic mice), Nannomys (African pygmy mice), Pyromys (Asian spiny mice), and Coelomys (Southeast Asian arboreal mice).^[11] This classification, based on molecular and morphological data, encompasses approximately 42 species as of 2023, though the total has been estimated at up to 43 in earlier phylogenetic analyses, with ongoing discoveries indicating higher cryptic diversity, particularly in Africa.^[11][12] Recent taxonomic revisions have focused on genetic assessments, confirming the monophyly of these subgenera while revealing new species and questioning some subspecies boundaries.^[6] As of 2024, phylogenetic studies continue to reveal cryptic diversity, particularly in Nannomys, with estimates suggesting up to 20 operational taxonomic units.^[6] The subgenus Mus includes the well-studied house mouse complex (M. musculus), distributed across Eurasia and introduced worldwide, with key subspecies including M. m. domesticus (western European house mouse, predominant in Western Europe and North America), M. m. musculus (eastern house mouse, found in Eastern Europe and Asia), and M. m. castaneus (Southeast Asian house mouse, native to South and Southeast Asia).^[11] Other species in this subgenus, such as the Algerian mouse (M. spretus) in North Africa and Iberia, the mound-building mouse (M. spicilegus) in Eastern Europe, the Macedonian mouse (M. macedonicus) in the Balkans and Anatolia, and the Cypriot mouse (M. cypriacus), endemic to Cyprus, highlight regional endemism.^[11] Recent whole-genome sequencing has challenged the validity of additional subspecies like M. m. bactrianus (from Pakistan) and M. m. helgolandicus (from Heligoland), finding them genetically indistinguishable from M. m. castaneus and M. m. domesticus, respectively, suggesting these should not be recognized as distinct taxa.^[13] The subgenus Nannomys exhibits the highest diversity, with 19 recognized species primarily in sub-Saharan Africa, characterized by small size and adaptations to diverse habitats from savannas to forests; phylogenetic studies reveal extensive cryptic diversity, potentially doubling the effective species count through molecular operational taxonomic units (MOTUs).^[6] Notable species include the African pygmy mouse (M. minutoides), widespread across Africa, and the setulose mouse (M. setulosus), restricted to West and Central Africa. Recent additions include a new species described from the isolated forests of southern Ethiopia in 2022, emphasizing the biogeographical uniqueness of highland ecosystems and belonging to this subgenus based on preliminary genetic data.^[14] Subgenera Pyromys and Coelomys are confined to Asia, with Pyromys featuring spiny-furred species like the Indian spiny mouse (M. saxicola) in arid regions of India and Pakistan, and Coelomys including arboreal forms such as the Sundaic mountain spiny mouse (M. pahari) in Southeast Asian highlands. These groups show less recent taxonomic activity compared to Mus and Nannomys, but molecular data continue to refine their boundaries within the genus.^[11]

Physical Description

Morphology and Anatomy

Species of the genus Mus exhibit typical rodent morphology, characterized by an elongated body with a pointed muzzle, small rounded ears, and a scaly tail that is generally longer than the head and body length.^[15] The fur is soft and dense, typically ranging from light brown to gray dorsally with lighter underparts, though coloration can vary slightly across species. This body plan facilitates movement through narrow spaces and burrows, common in their habitats.^[3] The dentition of Mus species follows the standard murid formula of I 1/1, C 0/0, P 0/0, M 3/3, resulting in 16 teeth total, with continuously growing incisors and molars featuring multiple cusps arranged in transverse rows, adapted for grinding plant and insect matter.^[16][17] The upper incisors feature a sharp notch, aiding in gnawing, while the molars have complex occlusal surfaces for efficient mastication. Sensory adaptations in Mus include large eyes suited for low-light conditions, prominent vibrissae (whiskers) that detect air currents and textures for navigation in confined environments, and a highly developed olfactory system for detecting food, predators, and conspecifics.^[15] These features enhance survival in nocturnal and crepuscular lifestyles. The skeletal structure of Mus species consists of lightweight, elongated bones and a flexible vertebral column, promoting agility and rapid maneuvers in tight spaces. The axial skeleton includes a robust skull with a broad zygomatic plate, while the appendicular skeleton supports quadrupedal locomotion with elongated limbs relative to body size.^[18]

Size and Variation

Species in the genus Mus exhibit a range of body sizes, typically characterized by head-body lengths of 5–10 cm, tail lengths of 5–12 cm, and weights of 10–30 g in common species such as M. musculus.^[15][19] For instance, adult M. musculus individuals have head-body lengths ranging from 65–103 mm, tail lengths from 60–104 mm, and weights from 12–39 g, reflecting adaptability to diverse environments.^[15][19][5] Variations occur across subgenera, with species in the subgenus Nannomys (African pygmy mice) being notably smaller, often weighing under 10 g.^[6] For example, M. minutoides has a head-body length of 40–72 mm, tail length of 27–57 mm, and weight of 3–12 g, while other Nannomys species range from 8–13 g.^[20][6] In contrast, species in the subgenus Pyromys (spiny mice), such as M. platythrix and M. saxicola, maintain sizes comparable to the Mus subgenus, with head-body lengths of 77–123 mm, tail lengths of 51–81 mm, and weights around 18–21 g, distinguished primarily by their spiny fur rather than extreme size differences.^[21][22] Sexual dimorphism in body size is present in some species, with males generally slightly larger than females.^[23] In M. musculus, adult males exhibit greater body mass and length compared to females, a pattern that emerges postnatally and persists in free-living populations.^[24] This dimorphism is subtle and heritable, contributing to intraspecific variation without overriding environmental influences.^[25] Geographic and subspecific variations further influence size, particularly in M. musculus, where individuals in temperate zones tend to be larger than those in tropical regions, aligning with ecogeographic patterns like Bergmann's rule.^[25] For example, subspecies such as M. m. domesticus in cooler climates show increased body mass compared to tropical forms like M. m. castaneus, with these differences persisting even in common rearing conditions due to genetic factors.^[25] Such variations underscore the genus's plasticity in response to latitudinal gradients.^[25]

Distribution and Habitat

Geographic Range

The genus Mus is predominantly native to Eurasia, Africa, and parts of Southeast Asia, with distributions varying by subgenus. The subgenus Mus, which includes the house mouse (M. musculus), is primarily distributed across Eurasia and North Africa, ranging from the Mediterranean Basin eastward to central Asia and the Indian subcontinent.^[3] In contrast, the subgenus Nannomys (African pygmy mice) is endemic to sub-Saharan Africa, with species occupying diverse regions from savannas to montane forests.^[6] The subgenus Pyromys is centered in the Indian subcontinent and extends into Southeast Asia, while the related subgenus Coelomys is similarly restricted to these areas, contributing to elevated species richness in southern and eastern Asia.^[26] Human activities have facilitated the global introduction of Mus species, particularly M. musculus, resulting in established populations across all continents except Antarctica. This species was introduced to the Americas in the early 16th century via European ships, spreading rapidly through colonial settlements and trade routes.^[27] Similarly, introductions to Australia and Oceania occurred during the colonial era, with genetic evidence tracing Australian populations to British Isles origins in the late 18th and early 19th centuries.^[28] These invasions have led to M. musculus becoming a cosmopolitan commensal, often outcompeting native rodents in human-modified landscapes. Notable hotspots of Mus diversity include the Indian subcontinent, where high species richness reflects the overlap of subgenera Mus, Pyromys, and Coelomys, encompassing at least 10 recognized species such as M. booduga, M. platythrix, and M. saxicola.^[29] In Africa, the Ethiopian highlands harbor diverse endemics within Nannomys, including recently described species like M. harennensis in isolated southern forests, underscoring the region's biogeographical uniqueness.^[7] Patterns of range expansion in Mus illustrate both natural and anthropogenic influences. In Europe, M. musculus domesticus underwent post-glacial recolonization approximately 10,000–15,000 years ago, originating from refugia in the Near East (modern-day Iran) and spreading westward via natural dispersal.^[30] Human-mediated invasions began around 10,000 BCE during the Neolithic period in the Near East, accelerating with agriculture and trade, which propelled M. musculus into new territories long before colonial expansions.^[31]

Habitat Preferences

Species of the genus Mus exhibit a wide range of habitat preferences, reflecting their adaptability across diverse ecosystems, though many show a strong association with human-modified environments. The house mouse (Mus musculus), unique within the genus, primarily occupies synanthropic habitats such as homes, farms, warehouses, and urban areas worldwide, where it thrives in close proximity to human activity; however, feral populations also inhabit wild settings including grasslands, agricultural fields, and forest edges.^[4] In natural environments, Mus species favor open and semi-open landscapes. Many Eurasian and African taxa prefer grasslands, scrublands, and forest margins, with species like the Algerian mouse (Mus spretus) commonly found in agroecosystems encompassing crops, orchards, and Mediterranean scrublands. The subgenus Nannomys, comprising African pygmy mice, predominantly inhabits savannas across sub-Saharan Africa, including arid Sahelian savannas for species such as Mus haussa and forest-savanna ecotones for Mus baoulei. In contrast, the subgenus Pyromys, native to South Asia, is adapted to rocky arid zones; for instance, the rock-loving mouse (Mus saxicola) occupies subtropical dry deciduous forests, grasslands, and rocky hillsides up to 1,000 m elevation, while the flat-haired mouse (Mus platythrix) favors uncultivated hilly areas with sandy, rocky, and gravelly substrates.^{[32][33][34][35]} Adaptations to extreme conditions enable Mus species to exploit marginal habitats. Burrowing behaviors allow survival in desert and semi-arid regions, as seen in some Nannomys taxa in sandy and stony deserts, while arboreal and climbing abilities support occupancy of tropical forest understories, particularly for forest-dwelling Nannomys like Mus cf. gratus in Congo Basin clearings. Altitudinally, Mus ranges from sea level to over 4,000 m, with Asian subspecies such as Mus musculus castaneus exhibiting genetic adaptations to high-elevation Himalayan environments above 2,500 m, including hypoxic conditions in mountainous grasslands and shrublands.^[33][36][37]

Behavior and Ecology

Social Structure and Activity Patterns

Species within the genus Mus typically exhibit solitary or small family group social structures, with adult males maintaining territories that they defend aggressively against intruders. In the house mouse (Mus musculus), social organization varies by subspecies and environmental conditions; for instance, M. m. domesticus forms tighter, more modular social units with stronger territorial boundaries, while M. m. musculus shows more intermixed interactions and weaker spatial separation, leading to higher rates of multiple paternity (0.11–0.42). These patterns promote resource partitioning and reduce conflict, though feral populations can include nomadic individuals during low-density periods. Some M. musculus populations engage in colonial nesting, where females share communal nests for pup care, contrasting with the more solitary habits of other Mus species like M. spicilegus, which build mound colonies but maintain individual territories.^[38] Activity patterns in Mus species are predominantly nocturnal, with individuals becoming more active immediately after dark onset and sustaining high levels of movement throughout the night, often tapering off 3–4 hours before dawn in wild-caught mice. This crepuscular-nocturnal rhythm is modulated by light masking, where exposure to light suppresses activity (negative masking) and darkness enhances it, particularly in response to predation risks that favor concealment during daylight hours. Laboratory strains of M. musculus (e.g., Swiss Webster and C57BL/6) display prolonged nighttime wakefulness, reaching near-100% activity in the early hours post-darkness, while wild populations adjust timing based on population density and environmental cues. These patterns ensure foraging and social interactions occur under cover of darkness, minimizing exposure to diurnal predators.^[39][40] Communication in Mus relies on multimodal signals, including ultrasonic vocalizations (USVs) in the 20–100 kHz range for alarm calls and courtship songs, which convey social status and attract mates without alerting predators. Male M. musculus produce complex USVs with syllable types such as frequency upsweeps and downsweeps during interactions with females or their pheromones, eliciting phonotactic responses from receptive females who prefer conspecific calls. Scent marking via urine deposits reinforces territorial boundaries and social hierarchies, with males increasing marking frequency in response to rivals or estrous cues, complementing acoustic signals in mate attraction and intruder deterrence. Across Mus species, USV characteristics differ spectrally and temporally (e.g., between M. musculus and M. spicilegus), aiding species recognition.^[41][42] Dominance hierarchies among males in Mus are established through agonistic displays, including chasing, lateral attacks, and biting, which resolve competitive interactions and stabilize group dynamics. In M. musculus, these hierarchies form linear ranks in group-housed settings, with dominant individuals gaining priority access to resources and mates, as measured by tube tests where winners emerge by forcing subordinates out. Aggressiveness levels, influenced by prior social experience and body weight, predict hierarchy position, with dominant males showing elevated urine marking and reduced submission. Such structures minimize energy expenditure on prolonged conflicts, though stability varies with population density.^[43][44]

Diet and Foraging

Species of the genus Mus are omnivorous, with diets primarily consisting of seeds, grains, and insects, though they opportunistically consume fruits, roots, leaves, stems, and occasionally carrion.^[45] In wild populations, such as the house mouse (Mus musculus), vegetable matter forms the bulk of intake, supplemented by invertebrates and small amounts of meat when available, allowing adaptation to diverse environments from grasslands to human settlements.^[15] Species in the subgenus Nannomys, including the African pygmy mouse (Mus minutoides), similarly rely on seeds and insects as main dietary components, reflecting their role in seed dispersal and insect control within African habitats.^[46] Foraging in Mus species involves opportunistic strategies, often conducted nocturnally to minimize predation risk and access resources like stored grains or ground-level seeds.^[4] Individuals retrieve and transport food to burrows, where they may cache surplus items for later use, though this behavior is less pronounced than in some other rodents.^[47] These raids on food sources, combined with brief ground-surface activity, enable efficient resource acquisition without extensive territorial defense during feeding.^[48] Ecologically, Mus species occupy a primarily herbivorous trophic level with carnivorous elements from insectivory and scavenging, serving as key prey for predators including owls (e.g., barn and tawny owls), snakes, and felids like domestic cats.^[15] This position integrates them into food webs as both consumers of plant and animal matter and vital sustenance for higher trophic levels. Adaptations for feeding include the absence of cheek pouches, relying instead on continuously growing incisors for efficient gnawing and processing of hard seeds and grains.^[49]

Reproduction and Life Cycle

Mating and Breeding Systems

Mating systems in the genus Mus vary across species and subgenera, influenced by ecological and social factors. Many species, such as the house mouse (Mus musculus) in the subgenus Mus, exhibit polygynous systems where a single male mates with multiple females.^[50] However, other species like Mus spicilegus show monogamous pair-bonding and cooperative breeding.^[51] In high-density populations of M. musculus, systems can shift toward promiscuity, with both sexes engaging in multiple matings, leading to increased multiple paternity within litters.^[52] This flexibility supports adaptive strategies based on population dynamics and resources.^[53] Courtship behaviors differ among species but often include behavioral displays and chemical signals. In several species of the subgenus Mus, such as M. musculus, M. spretus, and M. spicilegus, males produce ultrasonic vocalizations described as "songs" in the 30–110 kHz range to attract females.^[42] These are accompanied by physical actions like chasing and mounting.^[54] Pheromones are important in some species; in M. musculus, male urinary scents including darcin trigger estrus synchronization via the Whitten effect.^[55] Breeding patterns vary by habitat and subgenus. In tropical regions, species in Nannomys (sub-Saharan Africa) and Asian subgenera often breed continuously year-round.^[4] In temperate zones, Eurasian species like M. musculus show seasonal breeding, peaking spring through fall.^[56] Litter sizes range from 1 to 12 pups across the genus, with higher averages of 4–12 in M. musculus (up to 10 litters annually under optimal conditions) and lower averages of 2–8 in Nannomys species like Mus minutoides.^[15][57]

Development and Lifespan

Gestation periods in Mus species typically last 18–24 days, producing altricial young that are blind, hairless, and dependent on maternal care; for example, 18–21 days in M. musculus.^[15][4] Newborn weights vary with species size, ranging from ~0.5–1.5 g across the genus (e.g., 1–1.5 g in M. musculus, ~0.7–1 g in M. minutoides).^[58][57] Pups remain in the nest, nursing during early vulnerability. Postnatal development is rapid, with milestones varying slightly by species. In M. musculus, fur develops at 2–4 days, ears open at 3–5 days, eyes at 10–14 days, weaning at ~3 weeks, and sexual maturity at 6–8 weeks.^[59][60][4] Similar patterns occur in other species, scaled to body size. Growth is exponential early on; weights increase from ~0.5–1.5 g at birth to 3–15 g by weaning, reaching adult sizes of 4–30 g (e.g., 10–15 g weaning to 15–25 g adult in M. musculus; ~3 g weaning to 5–12 g adult in M. minutoides).^[58][57] In the wild, lifespans average 1–3 years across species due to predation and environmental factors, extending to 2–4 years in captivity.^[15] Juvenile mortality is high in wild populations, often 50–80% before independence in M. musculus from predation, starvation, or disturbances.^[61]

Evolutionary History

Fossil Record

The fossil record of the genus Mus traces its origins to precursor forms in the Middle Miocene, with the earliest representatives of the murine lineage appearing around 15–11 million years ago in Europe and Asia. The genus Progonomys is widely recognized as a key precursor, characterized by primitive dental morphology that bridges early murids and modern Mus, with fossils documented from late Miocene deposits (approximately 12–7 million years ago) across southern Europe, the Levant, and Asia Minor. These finds, including isolated teeth and mandibles from sites like the Siwalik Hills in Pakistan and Batallones in Spain, indicate an initial dispersal from southern Asian origins toward western Eurasia.^[62][63][64] Diversification of the genus Mus accelerated during the Late Miocene, coinciding with climatic shifts and habitat expansions across Africa and Eurasia, leading to a radiation of species adapted to diverse environments. In Africa, the earliest definitive Mus fossils date to the early to middle Pliocene (around 5–3 million years ago) in the Omo Valley of Ethiopia, represented by small-bodied forms with advanced occlusal patterns suggestive of grassland adaptations. Eurasian records from the same period include species from the Siwalik sequence in India and Pakistan, such as early Mus with morphologies akin to modern Mus musculus ancestors, marking a transition to more specialized house mouse-like traits. A notable Pliocene species is the unnamed ancestor of the house mouse from late Pliocene sediments (about 3.5 million years ago) in the Indian Siwaliks, highlighting regional endemism before broader Quaternary dispersals.^[6][65][66] The Quaternary period records significant post-Ice Age expansions of Mus lineages, particularly M. musculus, with fossils appearing around 10,000 years ago in archaeological sites across Europe and Asia, linked to human-mediated dispersal during the Neolithic. These remains, often from cave and settlement deposits, show morphological continuity with modern populations and reflect rapid colonization of anthropogenic habitats following the Last Glacial Maximum. Extinct species from this era include Mus-like forms resembling M. bactrianus in Central Asian Pleistocene sites, such as those in the Afghan-Tadjik Depression, where dental fossils indicate larger-bodied, arid-adapted variants that disappeared amid late Holocene environmental changes.^[31][67]

Genetic and Phylogenetic Insights

Mitochondrial DNA analyses have elucidated the biogeographic origins of key subgenera within the genus Mus. For the subgenus Nannomys, comprising African pygmy mice, comprehensive sequencing of mitochondrial genes such as cytochrome b from over 650 individuals across sub-Saharan Africa has revealed deep phylogenetic divergence and high cryptic diversity, supporting an ancient African origin dating back to approximately 7–8 million years ago (Ma).^[33] In contrast, the subgenus Pyromys, which includes species endemic to the Indian subcontinent and Southeast Asia, exhibits mitochondrial haplotypes indicative of an Asian cradle of diversification, with basal splits estimated around 5–6 Ma based on combined mitochondrial and nuclear markers.^[68] These findings highlight how vicariance and dispersal events shaped the early radiation of Mus subgenera, with Nannomys remaining largely confined to Africa while Pyromys adapted to tropical Asian environments.^[69] Hybrid zones between closely related taxa in the genus Mus provide critical insights into the genetic barriers maintaining species boundaries. A prominent example is the narrow hybrid zone in central Europe between Mus musculus musculus (eastern house mouse) and M. m. domesticus (western house mouse), where genomic scans reveal steep clines in allele frequencies, particularly on the X chromosome, indicating Dobzhansky-Muller incompatibilities that reduce hybrid fitness.^[70] Whole-genome analyses across this zone show bidirectional but asymmetric introgression, with autosomes exchanging genes more freely than sex-linked loci, underscoring the role of chromosomal and epistatic barriers in reinforcing reproductive isolation despite ongoing contact.^[71] Such zones illustrate how postzygotic selection sustains genetic differentiation in Mus, even in the face of secondary admixture.^[72] The genome of Mus species, averaging approximately 3 pg of DNA per diploid cell, has been instrumental in advancing phylogenetic and comparative studies. The house mouse (M. musculus), a cornerstone model organism, had its genome fully sequenced in 2002 using a whole-genome shotgun approach, yielding a high-quality assembly of about 2.6 gigabases that facilitated initial insights into mammalian evolution and conserved synteny. Subsequent updates in the 2020s, including the GRCm39 assembly, incorporated long-read sequencing to resolve repetitive regions and structural variants, enhancing resolution for phylogenetic reconstructions across the genus.^[73] Speciation events in Mus are characterized by rapid radiations, as dated by molecular clock calibrations. Nuclear genes such as interphotoreceptor retinoid-binding protein (IRBP) and recombination-activating gene 1 (RAG1) yield divergence estimates placing the origin of the four main subgenera (Mus, Coelomys, Nannomys, and Pyromys) at 5–6 Ma, followed by accelerated lineage splitting within subgenera around 2–3 Ma, likely driven by Pleistocene climatic oscillations and habitat fragmentation.^[68] These clock-based timelines, calibrated against fossil constraints, reveal pulses of diversification that align with the genus's global expansion, emphasizing the interplay of allopatric isolation and adaptive divergence in generating Mus biodiversity.^[69]

Relationship to Humans

Role in Research and Medicine

The genus Mus, particularly M. musculus, has been a cornerstone model organism in biomedical research since the early 1900s, owing to its genetic tractability and physiological similarities to humans. The development of inbred strains revolutionized genetics studies; Clarence C. Little established the first such strain, DBA, in 1909 using coat color markers to track inheritance, enabling controlled experiments on Mendelian traits. By 1921, the C57BL/6 strain—derived from black-furred mice bred by Abby Lathrop—was created, becoming one of the most widely used due to its well-characterized genome and robustness in experimental settings, accounting for over 14% of inbred strain usage in research.^[74][75][76] These strains underpin diverse applications in cancer research, immunology, and neuroscience. In oncology, mouse models facilitate the study of tumorigenesis and therapeutic responses; for instance, genetically engineered mice with targeted oncogene activations mimic human cancers, aiding in the evaluation of immunotherapies like checkpoint inhibitors. Immunologically, humanized mouse models, where immune systems are engrafted with human cells, test vaccine efficacy and antibody responses against pathogens, revealing mechanisms of T-cell activation and tolerance. In neuroscience, mice enable investigations into synaptic plasticity and neurodegeneration, with C57BL/6 strains commonly used to model Alzheimer's pathology through amyloid-beta plaque induction.^[77]00041-9)^[78] Genome editing technologies have further amplified the utility of Mus models since 2013, when CRISPR-Cas9 was first adapted for precise modifications in mouse zygotes, allowing simultaneous disruption of multiple genes like Tet1, Tet2, and Tet3 to study embryonic development. This breakthrough enabled rapid creation of knock-in and knock-out strains, accelerating research into gene functions and disease modeling without lengthy breeding cycles. In behavioral studies, mice undergo operant conditioning paradigms to probe learning and addiction; for example, self-administration tasks where rodents press levers for cocaine or ethanol infusions model reinforcement escalation and relapse, with progressive ratio schedules quantifying motivational breakpoints to dissect neural circuits involved in decision-making.00467-4)^[79][80] Recent advances in the 2020s have leveraged mouse-derived stem cells for organoid cultures, providing three-dimensional platforms that recapitulate tissue architecture for drug testing and disease simulation. Protocols refined from mouse intestinal Lgr5+ stem cells now support vascularized organoids for organs like the kidney and brain, enhancing maturation and enabling high-throughput screening of therapeutics, such as modulators for cystic fibrosis or Parkinson's models. These innovations bridge in vitro and in vivo research, offering scalable alternatives to whole-animal studies while preserving physiological fidelity.^[81]

Impact as Pests and Health Risks

Species of the genus Mus, particularly the house mouse (Mus musculus), are major agricultural pests due to their consumption and contamination of stored grains and crops. Rodents, including house mice, are estimated to destroy or damage up to 20% of the global food supply annually through direct feeding and waste production, exacerbating food insecurity in developing regions.^[82] In stored grain facilities, house mice can infest silos and warehouses, leading to significant quantitative losses; for instance, a single mouse consumes about 3 grams of food per day and contaminates up to 10 times that amount with urine and feces, promoting mold growth and spoilage.^[83] Outbreaks amplify this impact, as seen in the 2021 Australian mouse plague across New South Wales and Queensland, where dense populations caused an estimated AUD 1 billion in agricultural losses, including destroyed crops, contaminated feed, and damaged farm infrastructure.^[84] House mice also pose substantial public health risks as vectors for zoonotic diseases. They transmit pathogens such as hantavirus through aerosolized excreta, leading to hantavirus pulmonary syndrome with a mortality rate of up to 38% in affected cases; while deer mice are primary carriers in North America, house mice can harbor and spread related hantaviruses in other regions.^[85][86] Leptospirosis, caused by Leptospira bacteria shed in mouse urine, contaminates water and soil, resulting in flu-like symptoms or severe kidney failure; studies confirm house mice as key reservoirs, with prevalence rates up to 86% in high-density populations.^[87] Similarly, salmonellosis spreads via fecal contamination of food and water, with house mice acting as reservoirs that maintain infection cycles in livestock and human environments, contributing to thousands of annual cases worldwide.^[88] Historically, commensal rodents including house mice facilitated the transmission of bubonic plague (Yersinia pestis) during pandemics like the Black Death, serving as flea hosts that amplified outbreaks in urban and rural settings, though black rats were dominant vectors.^[89] The economic burden of Mus species as pests is immense, encompassing direct damages, contamination cleanup, and control efforts. Globally, invasive rodents have incurred at least US$3.6 billion in reported costs from 1930 to 2022, with over 90% attributed to agricultural impacts and the remainder to management like rodenticides and trapping; annual extrapolated losses likely reach billions when including unreported damages.^[90] In the United States alone, rodent infestations, driven largely by house mice, cause approximately $19 billion in yearly economic losses across agriculture, property, and health sectors.^[91] Control measures, including chemical rodenticides, account for a significant portion of these costs but raise environmental concerns due to secondary poisoning of non-target wildlife. Despite their pest status, trained house mice have been utilized since the 2000s in olfactory detection tasks, such as identifying explosives or pathogens in controlled settings, highlighting their sensory capabilities though such applications remain limited compared to their widespread negative impacts.^[92]