Rodentia

Rodentia (from the Latin rodere, "to gnaw") is the largest and most speciose order of mammals (Mammalia), comprising more than 2,600 described extant species across ~35 families—accounting for approximately 40% of all living mammalian species on Earth. Together with its sister order Lagomorpha (~105 species of rabbits, hares, and pikas), Rodentia forms the cohort Glires within the Boreoeutherian superorder Euarchontoglires (making mice, rats, and squirrels closer evolutionary relatives of primates and humans than of dogs, cats, or cows!).

Ranging across four orders of magnitude in body mass—from the Baluchistan pygmy jerboa (Salpingotus michaelis, 3.5 grams) and Eurasian harvest mouse (Micromys minutus, 5 g) to the semi-aquatic South American capybara (Hydrochoerus hydrochaeris, 50–80 kg) and the extinct Pliocene giant rodent *Josephoartigasia monesi*† (~1,000 kg, the size of a bison!)—rodents include humanity's premier biomedical model organisms: the house mouse (Mus musculus), brown rat (Rattus norvegicus), guinea pig (Cavia porcellus), and naked mole-rat (Heterocephalus glaber).

1. One Pair of Rootless, Continuously Growing Chiseling Incisors (Hypselodonty): Every rodent possesses a single pair of enlarged upper and lower incisors (I 1/1)—distinguishing Rodentia immediately from Lagomorpha (rabbits and pikas), which fall inside Duplicidentata because they retain a second pair of small peg-like upper incisors directly behind their main front incisors (I 2/1). How does a rodent's incisor gnaw through hardwood trees (beavers Castor canadensis), nutshells, concrete, and even lead pipes without wearing down to a nub or going dull?
   • Cervical Loop Epithelial Stem-Cell Niche: Rodent incisors have open, unsealed roots housing a permanent niche of Sox2⁺ / FGF10-maintained dental epithelial stem cells (the cervical loop, studied by Irma Thesleff and Ophir D. Klein) that continuously proliferate to push the tooth forward at 2 to 5 millimeters per week throughout the animal's life;
   • Asymmetric Differential Wear (Self-Sharpening Chisel): Enamel is deposited exclusively on the front (labial) face of the incisor, while the back (lingual) face consists of softer dentine. As the upper and lower incisors grind against one another, the softer lingual dentine wears away faster than the hard front enamel plate, automatically maintaining a razor-sharp beveled chisel edge!
   • Iron-Substituted Ferrihydrite / Goethite Orange Enamel: Why are the front teeth of beavers, squirrels, and rats bright orange or reddish-brown? As demonstrated using atom-probe tomography by Lyle M. Gordon, Derk Joester, and colleagues in Science (2015), ameloblasts at the outer surface of rodent enamel replace magnesium ions in the amorphous intergranular boundary phase between hydroxyapatite nanocrystals with iron (Fe³⁺ oxyhydroxide / ferrihydrite)—making iron-pigmented beaver enamel both harder and significantly more resistant to acid dissolution and mechanical fracture than human or fluoride-treated enamel!
2. Complete Loss of Canine Teeth and the Cheek-Fold Diastema: All rodents lack canine teeth and anterior premolars (C 0/0), leaving a wide toothless gap (diastema) between the gnawing incisors and the grinding cheek teeth (molars and premolars). During gnawing on inedible wood or soil, muscular folds of the hairy cheek (inflexa pellita) tuck inward through the diastema behind the incisors to seal off the mouth cavity, preventing wood chips or dirt from being swallowed!
3. Evolution of the Four Zygomasseteric Jaw-Muscle Architectures: In rodents, the temporalis muscle is reduced while the masseter muscle is extensively expanded and subdivided into three layers (superficial masseter, lateral masseter, and medial masseter) that pull the lower jaw forward and upward for propulsive gnawing and grinding. Across suborders, rodents evolved four distinct skull geometries to expand the origin of the masseter muscle onto the rostrum and through the infraorbital foramen:

Why has the East African subterranean naked mole-rat (Heterocephalus glaber) (a hairless, 35-gram hystricomorph rodent living in sealed underground tunnel systems of up to 300 individuals) become one of the most intensively studied mammals in 21st-century biomedicine?

1. Mammalian Eusociality: As discovered by Jennifer U. M. Jarvis (1981), naked mole-rats (and Damaraland mole-rats, Fukomys damarensis) are the only known eusocial mammals—convergent with ants, bees, and termites: a single dominant reproductive queen (whose lumbar vertebrae actually elongate after she ascends to queenship!) and 1–3 breeding males produce all offspring, while the remaining 95%+ of the colony serve as reproductively suppressed, non-breeding worker and soldier castes.
2. 37-Year Lifespan and High-Molecular-Mass Hyaluronic Acid Cancer Resistance: Whereas a 30-gram house mouse lives 2–3 years and ~70% die of cancer, naked mole-rats live over 37 to 40 years with negligible physiological senescence and almost zero spontaneous cancer. In 2009 and 2013, Vera Gorbunova, Andrei Seluanov, Xiao Tian, and colleagues discovered that naked mole-rat fibroblasts secrete an ultra-high-molecular-mass hyaluronic acid (vHMM-HA, 6 to 12 megadaltons—five times larger than human or mouse hyaluronan!) synthesized by a uniquely mutated Hyaluronan Synthase 2 (HAS2). Binding to the CD44 receptor and activating the p16^INK4a + p27^KIP1 tumor-suppressor cascade, this dense vHMM-HA matrix triggers early contact inhibition the moment cells crowd together, arresting tumor growth (and when naked mole-rat HAS2 was engineered into transgenic mice by Zhang et al., 2023, it reduced mouse cancer incidence and extended median mouse lifespan!).
3. Plant-Like Fructose-Driven Glycolysis During 18 Minutes of Complete Anoxia: Because hundreds of mole-rats crowd inside unventilated underground burrows where O₂ drops to 6% and CO₂ exceeds 10%, Thomas J. Park, Gary R. Lewin, and colleagues (Science, 2017) discovered that naked mole-rats can survive 18 minutes in 0% oxygen (pure nitrogen gas) without any brain damage! When deprived of oxygen, the naked mole-rat brain upregulates the fructose transporter GLUT5 and the enzyme ketohexokinase (KHK) to pump fructose directly into glycolysis at the dihydroxyacetone phosphate / glyceraldehyde-3-phosphate step—bypassing the low-pH phosphofructokinase (PFK1) feedback block that shuts down glucose metabolism in hypoxic human brains!

How can male spiny mice (Acomys) and mole-voles (Ellobius) develop as fertile males after completely losing their Y chromosome and SRY gene?

In 99.9% of placental mammals, male testis development is triggered by the SRY (Sex-Determining Region Y) transcription factor on the Y chromosome, which binds an enhancer upstream of the autosomal gene SOX9 to turn embryonic gonads into testes. Remarkably, Japanese Ryukyu spiny rats (Tokudaia osimensis) and Transcaucasian mole-voles (Ellobius lutescens and E. talpinus) completely lost their entire Y chromosome and SRY gene (both males and females have an identical XO or XX karyotype!). In 2022, Miho Terao, Shuji Takada, Asato Kuroiwa, and colleagues solved how Tokudaia osimensis makes males without a Y chromosome: males carry a tandemly duplicated 17-kilobase enhancer (Enh14) upstream of Sox9 on an autosome (Chromosome 3), turning Chromosome 3 into a de novo proto-sex chromosome that activates Sox9 and triggers testis development in the absence of SRY!

1. Jarvis, J. U. M. (1981). Eusociality in a mammal: Cooperative breeding in naked mole-rat colonies. Science, 212(4494), 571–573. doi:10.1126/science.7209555
2. Seifert, A. W., Kiama, S. G., Seifert, M. G., Goheen, J. R., Palmer, T. M., & Maden, M. (2012). Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature, 489(7417), 561–565. doi:10.1038/nature11499
3. Tian, X., Azpurua, J., Hine, C., Vaidya, A., Myakishev-Rempel, M., Ablaeva, J., ... & Seluanov, A. (2013). High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature, 499(7458), 346–349. doi:10.1038/nature12234
4. Gordon, L. M., Cohen, M. J., MacRenaris, K. W., Pasteris, J. D., Seda, T., & Joester, D. (2015). Amorphous intergranular phases control the properties of rodent tooth enamel. Science, 347(6223), 746–750. doi:10.1126/science.1258950
5. Park, T. J., Reznick, J., Peterson, B. L., Blass, G., Omerbašić, D., Bennett, N. C., ... & Lewin, G. R. (2017). Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat. Science, 356(6335), 307–311. doi:10.1126/science.aab3896
6. Terao, M., Ogawa, Y., Takada, S., Kajitani, R., Okuno, M., Mochimaru, Y., ... & Kuroiwa, A. (2022). Turnover of mammal sex chromosomes in the Sry-deficient Amami spiny rat is due to duplication of a Sox9 enhancer. Proceedings of the National Academy of Sciences, 119(49), e2211574119. doi:10.1073/pnas.2211574119