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      Digital dissection of the masticatory muscles of the naked mole-rat, Heterocephalus glaber (Mammalia, Rodentia)

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      1 , , 2
      PeerJ
      PeerJ Inc.
      Naked mole-rat, Masticatory muscles, MicroCT, Virtual reconstruction, Bathyergidae, Rodents

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          Abstract

          The naked mole-rat, Heterocephalus glaber, of the family Bathyergidae is a subterranean rodent that feeds on underground roots and tubers and digs extensive tunnel systems with its incisors. It is a highly unusual mammal with regard to its social structure, longevity, pain insensitivity and cancer resistance, all of which have made it the subject of a great deal of research in recent years. Yet, much of the basic anatomy of this species remains undocumented. In this paper, we describe the morphology of the jaw-closing musculature of the naked mole-rat, as revealed by contrast-enhanced micro-computed tomography. This technique uses an iodine stain to enable the imaging of soft tissues with microCT. The iodine-enhanced scans were used to create 3D reconstructions of the naked mole-rat masticatory muscles from which muscle masses were calculated. The jaw-closing musculature of Heterocephalus glaber is relatively very large compared to other rodents and is dominated by the superficial masseter, the deep masseter and the temporalis. The temporalis in particular is large for a rodent, covering the entirety of the braincase and much of the rear part of the orbit. The morphology of the masseter complex described here differs from two other published descriptions of bathyergid masticatory muscles, but is more similar to the arrangement seen in other rodent families. The zygomaticomandibularis (ZM) muscle does not protrude through the infraorbital foramen on to the rostrum and thus the naked mole-rat should be considered protrogomorphous rather than hystricomorphous, and the morphology is consistent with secondarily lost hystricomorphy as has been previously suggested for Bathyergidae. Overall, the morphology of the masticatory musculature indicates a species with a high bite force and a wide gape–both important adaptations for a life dominated by digging with the incisors.

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          Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat.

          The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition." Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27(Kip1). In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16(Ink4a), and regular contact inhibition is controlled by p27(Kip1). We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.
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            The naked mole-rat: a new long-living model for human aging research.

            Tremendous variation in maximum life span among species overshadows modest increases in longevity resulting from experimental manipulation. Few aging studies focus on long-lived mammals even though these species may expose mechanisms involved in resisting aging. Naked mole-rats (NMRs approximately 35 grams) are the longest-living (>28.3 years) rodents known. This review describes their biology and potential use in aging research. Lifestyle features concur with most evolutionary theories with the exception of the disposable soma theory. Indeed, maximum life span is similar in breeders and nonbreeders, and these highly fecund animals reproduce until they die. Shared characteristics with calorie-restricted, methionine-restricted, and dwarf mice models of extended longevity include reduced body temperature; reduced thyroid, and blood glucose concentrations; and low glycated hemoglobin; in addition to reduced incidence of cancer. Young naked mole-rats surprisingly have high levels of accrued oxidative damage. With their similar longevity quotient to humans, these rodents may provide a novel opportunity to examine mechanisms modulating aging.
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              Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades

              Background Rodentia is the most diverse order of placental mammals, with extant rodent species representing about half of all placental diversity. In spite of many morphological and molecular studies, the family-level relationships among rodents and the location of the rodent root are still debated. Although various datasets have already been analyzed to solve rodent phylogeny at the family level, these are difficult to combine because they involve different taxa and genes. Results We present here the largest protein-coding dataset used to study rodent relationships. It comprises six nuclear genes, 41 rodent species, and eight outgroups. Our phylogenetic reconstructions strongly support the division of Rodentia into three clades: (1) a "squirrel-related clade", (2) a "mouse-related clade", and (3) Ctenohystrica. Almost all evolutionary relationships within these clades are also highly supported. The primary remaining uncertainty is the position of the root. The application of various models and techniques aimed to remove non-phylogenetic signal was unable to solve the basal rodent trifurcation. Conclusion Sequencing and analyzing a large sequence dataset enabled us to resolve most of the evolutionary relationships among Rodentia. Our findings suggest that the uncertainty regarding the position of the rodent root reflects the rapid rodent radiation that occurred in the Paleocene rather than the presence of conflicting phylogenetic and non-phylogenetic signals in the dataset.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ Inc. (San Francisco, USA )
                2167-8359
                17 June 2014
                2014
                : 2
                : e448
                Affiliations
                [1 ]Hull York Medical School, University of Hull , Hull, UK
                [2 ]School of Biological and Chemical Sciences, Queen Mary University of London , UK
                Article
                448
                10.7717/peerj.448
                4081180
                25024917
                c13d98ea-4dbb-4205-a5bb-6d462d6a2914
                © 2014 Cox and Faulkes

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 15 April 2014
                : 3 June 2014
                Funding
                There was no external funding for this work.
                Categories
                Evolutionary Studies
                Zoology
                Anatomy and Physiology

                naked mole-rat,masticatory muscles,microct,virtual reconstruction,bathyergidae,rodents

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