Spalax Research Articles

Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology.

Simple SummaryBlind mole rats (BMR) (Spalax, Nannospalax sp.) are extraordinary organisms with cancer resistance and a long lifespan for their size. Cellular senescence is a condition in which cells cease dividing irreversibly and secrete proinflammatory cytokines. To understand the mechanisms behind their superior traits, we utilized transcriptomics and proteomics tools in senescent BMR cells to compare them to similarly sized mice. The results revealed the alterations in Janus kinase (JAK) signaling and the cytokine-mediated pathway during the cellular senescence process in BMRs. These findings might reveal the novel mechanisms behind the unique biology of BMRs through cytokine-mediated adaptations.The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK–STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK–STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK–STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.

Динаміка просторового розподілу, рийна діяльність та кормозапасання у сліпака східного (Spalax microphthalmus)

Original data on the burrowing and foraging activities of the greater blind mole rat (Spalax microphthalmus), which is distributed in the east of Ukraine, are generalised. The population density of this species depends directly on the amount of available food resources at the respective sites. The strategy of food storage forms according to the amount and type of available plant resources and depending on the preservation of natural habitat of mole rats. Their appearance in gardens and homesteads is related to anthropogenic changes of the environment at the dwelling sites of mole rats. The seasonal dynamics of their burrowing activity is well pronounced and includes the creation of a branching system of tunnels in the period of active vegetation of plants as well as the relocation or resettlement of animals in various habitats during the year, their lifetime, and population cycle. The length of tunnels, structure of burrows, and the structure of branched underground galleries are regulated by the density and spatial distribution of food resources. Based on the results of our study, specific features of the activity of the greater blind mole rat during various seasons of the years are described, including their active relocation both underground and on the surface, their burrowing at different horizons, the use of a great variety of food and the volumes of their storage for periods when the vegetation of plants ceases. Features of biotopic distribution and food storage of the greater blind mole rat are described in general and in relation to the species’ expansion into anthropogenically transformed parts of its range, including areas nearby to human settlements. The distribution of storage chambers is analysed, of both temporal chambers near the surface and deep-lying chambers, the ratio of which is about 3 : 1. The storage chambers often contain garden vegetables, although it is related not only to the preferences of mole rats, which are obvious too, but also to the fact that information about the storage chambers (especially deep-lying ones) is usually reported by people combating the mole rats for the stolen harvest. The average volume of low-lying chambers is 5–10 kg (1.0–1.5 buckets), whereas the average volume of deep-lying chambers is 20–30 kg. Data on the content of storage chambers revealed both in homesteads and natural or nearly natural sites are generalised.

Alone, in the dark: The extraordinary neuroethology of the solitary blind mole rat.

On the social scale, the blind mole rat (BMR; Spalax ehrenbergi) is an extreme. It is exceedingly solitary, territorial, and aggressive. BMRs reside underground, in self-excavated tunnels that they rarely leave. They possess specialized sensory systems for social communication and navigation, which allow them to cope with the harsh environmental conditions underground. This review aims to present the blind mole rat as an ideal, novel neuroethological model for studying aggressive and solitary behaviors. We discuss the BMR’s unique behavioral phenotype, particularly in the context of ‘anti-social’ behaviors, and review the available literature regarding its specialized sensory adaptations to the social and physical habitat. To date, the neurobiology of the blind mole rat remains mostly unknown and holds a promising avenue for scientific discovery. Unraveling the neural basis of the BMR’s behavior, in comparison to that of social rodents, can shed important light on the underlying mechanisms of psychiatric disorders in humans, in which similar behaviors are displayed.

Gene losses may contribute to subterranean adaptations in naked mole-rat and blind mole-rat

BackgroundNaked mole-rats (Heterocephalus glaber, NMRs) and blind mole-rats (Spalax galili, BMRs) are representative subterranean rodents that have evolved many extraordinary traits, including hypoxia tolerance, longevity, and cancer resistance. Although multiple candidate loci responsible for these traits have been uncovered by genomic studies, many of them are limited to functional changes to amino acid sequence and little is known about the contributions of other genetic events. To address this issue, we focused on gene losses (unitary pseudogenes) and systematically analyzed gene losses in NMRs and BMRs, aiming to elucidate the potential roles of pseudogenes in their adaptation to subterranean lifestyle.ResultsWe obtained the pseudogene repertoires in NMRs and BMRs, as well as their respective aboveground relatives, guinea pigs and rats, on a genome-wide scale. As a result, 167, 139, 341, and 112 pseudogenes were identified in NMRs, BMRs, guinea pigs, and rats, respectively. Functional enrichment analysis identified 4 shared and 2 species-specific enriched functional groups (EFGs) in subterranean lineages. Notably, the pseudogenes in these EFGs might be associated with either regressive (e.g., visual system) or adaptive (e.g., altered DNA damage response) traits. In addition, several pseudogenes including TNNI3K and PDE5A might be associated with specific cardiac features observed in subterranean lineages. Interestingly, we observed 20 convergent gene losses in NMRs and BMRs. Given that the functional investigations of these genes are generally scarce, we provided functional evidence that independent loss of TRIM17 in NMRs and BMRs might be beneficial for neuronal survival under hypoxia, supporting the positive role of eliminating TRIM17 function in hypoxia adaptation. Our results also suggested that pseudogenes, together with positively selected genes, reinforced subterranean adaptations cooperatively.ConclusionsOur study provides new insights into the molecular underpinnings of subterranean adaptations and highlights the importance of gene losses in mammalian evolution.

New insights into the relevance of mobile DNA to cancer resistance in blind mole rats: new lessons for cancer therapy.

New insights into the relevance of mobile DNA to cancer resistance in blind mole rats: new lessons for cancer therapy.

A Cytogenetic and Morphological Study on Nannospalax ehrenbergi in Adana (Ceyhan) Province

This study was conducted to explain the karyological analysis and morphological characteristics of blind mole rat samples collected from Ceyhan, Adana in Turkey. The chromosomes of the blind mole rat samples were stained and analysed using conventional methods. The chromosomes were defined according to centromere positions by processing photographs of metaphase cells. The karyotype of Nannospalax ehrenbergi showed 53 chromosomes (2n=53) and fundamental number of chromosomal arms NF=66 and the number of autosomal arms NFa= 62. The karyotype showed a hybrid individual. X and Y chromosomes were determined as metacentric and acrocentric, respectively. The autosomal set had 5 (+1 single homologous) pairs of metacentric/submetacentric and 20 pairs of acrocentric. Morphological studies were carried out on two male Nannospalax ehrenbergi skulls from Adana province. Lengths of three external (height, hindfoot length and weights (gr)) and 24 cranial morphological points on skulls were measured using an electronic caliper. This was the first study in which 2n=53 NF=66 population was determined from Ceyhan. This form was described as a hybrid form. The portion behind the palate (os palatinum) has no a sharply defined styloid process.

Glutamine Homeostasis and Its Role in the Adaptive Strategies of the Blind Mole Rat, Spalax.

Oxidative metabolism is fine-tuned machinery that combines two tightly coupled fluxes of glucose and glutamine-derived carbons. Hypoxia interrupts the coordination between the metabolism of these two nutrients and leads to a decrease of the system efficacy and may eventually cause cell death. The subterranean blind mole rat, Spalax, is an underexplored, underground, hypoxia-tolerant mammalian group which spends its life under sharply fluctuating oxygen levels. Primary Spalax cells are an exceptional model to study the metabolic strategies that have evolved in mammals inhabiting low-oxygen niches. In this study we explored the metabolic frame of glutamine (Gln) homeostasis in Spalax skin cells under normoxic and hypoxic conditions and their impacts on the metabolism of rat cells. Targeted metabolomics employing liquid chromatography and mass spectrometry (LC-MS) was used to track the fate of heavy glutamine carbons (13C5 Gln) after 24 h under normoxia or hypoxia (1% O2). Our results indicated that large amounts of glutamine-originated carbons were detected as proline (Pro) and hydroxyproline (HPro) in normoxic Spalax cells with a further increase under hypoxia, suggesting a strategy for reduced Gln carbons storage in proteins. The intensity of the flux and the presence of HPro suggests collagen as a candidate protein that is most abundant in animals, and as the primary source of HPro. An increased conversion of αKG to 2 HG that was indicated in hypoxic Spalax cells prevents the degradation of hypoxia-inducible factor 1α (HIF-1α) and, consequently, maintains cytosolic and mitochondrial carbons fluxes that were uncoupled via inhibition of the pyruvate dehydrogenase complex. A strong antioxidant defense in Spalax cells can be attributed, at least in part, to the massive usage of glutamine-derived glutamate for glutathione (GSH) production. The present study uncovers additional strategies that have evolved in this unique mammal to support its hypoxia tolerance, and probably contribute to its cancer resistance, longevity, and healthy aging.

Maintenance of genome sequence integrity in long- and short-lived rodent species.

DNA mutations in somatic cells have been implicated in the causation of aging, with longer-lived species having a higher capacity to maintain genome sequence integrity than shorter-lived species. In an attempt to directly test this hypothesis, we used single-cell whole-genome sequencing to analyze spontaneous and bleomycin-induced somatic mutations in lung fibroblasts of four rodent species with distinct maximum life spans, including mouse, guinea pig, blind mole-rat, and naked mole-rat, as well as humans. As predicted, the mutagen-induced mutation frequencies inversely correlated with species-specific maximum life span, with the greatest difference observed between the mouse and all other species. These results suggest that long-lived species are capable of processing DNA damage in a more accurate way than short-lived species.

Comprehensive Analysis of 13C6 Glucose Fate in the Hypoxia-Tolerant Blind Mole Rat Skin Fibroblasts.

The bioenergetics of the vast majority of terrestrial mammals evolved to consuming glucose (Glc) for energy production under regular atmosphere (about 21% oxygen). However, some vertebrate species, such as aquatic turtles, seals, naked mole rat, and blind mole rat, Spalax, have adjusted their homeostasis to continuous function under severe hypoxic environment. The exploration of hypoxia-tolerant species metabolic strategies provides a better understanding of the adaptation to hypoxia. In this study, we compared Glc homeostasis in primary Spalax and rat skin cells under normoxic and hypoxic conditions. We used the targeted-metabolomics approach, utilizing liquid chromatography and mass spectrometry (LC-MS) to track the fate of heavy Glc carbons (13C6 Glc), as well as other methodologies to assist the interpretation of the metabolic landscape, such as bioenergetics profiling, Western blotting, and gene expression analysis. The metabolic profile was recorded under steady-state (after 24 h) of the experiment. Glc-originated carbons were unequally distributed between the cytosolic and mitochondrial domains in Spalax cells compared to the rat. The cytosolic domain is dominant apparently due to the hypoxia-inducible factor-1 alpha (HIF-1α) mastering, since its level is higher under normoxia and hypoxia in Spalax cells. Consumed Glc in Spalax cells is utilized for the pentose phosphate pathway maintaining the NADPH pool, and is finally harbored as glutathione (GSH) and UDP-GlcNAc. The cytosolic domain in Spalax cells works in the semi-uncoupled mode that limits the consumed Glc-derived carbons flux to the tricarboxylic acid (TCA) cycle and reduces pyruvate delivery; however, it maintains the NAD+ pool via lactate dehydrogenase upregulation. Both normoxic and hypoxic mitochondrial homeostasis of Glc-originated carbons in Spalax are characterized by their massive cataplerotic flux along with the axis αKG→Glu→Pro→hydroxyproline (HPro). The product of collagen degradation, HPro, as well as free Pro are apparently involved in the bioenergetics of Spalax under both normoxia and hypoxia. The upregulation of 2-hydroxyglutarate production detected in Spalax cells may be involved in modulating the levels of HIF-1α. Collectively, these data suggest that Spalax cells utilize similar metabolic frame for both normoxia and hypoxia, where glucose metabolism is switched from oxidative pathways (conversion of pyruvate to Acetyl-CoA and further TCA cycle processes) to (i) pentose phosphate pathway, (ii) lactate production, and (iii) cataplerotic pathways leading to hexosamine, GSH, and HPro production.

The hypoxia adaptation of small mammals to plateau and underground burrow conditions.

Oxygen is one of the important substances for the survival of most life systems on the earth, and plateau and underground burrow systems are two typical hypoxic environments. Small mammals living in hypoxic environments have evolved different adaptation strategies, which include increased oxygen delivery, metabolic regulation of physiological responses and other physiological responses that change tissue oxygen utilization. Multi‐omics predictions have also shown that these animals have evolved different adaptations to extreme environments. In particular, vascular endothelial growth factor (VEGF) and erythropoietin (EPO), which have specific functions in the control of O2 delivery, have evolved adaptively in small mammals in hypoxic environments. Naked mole‐rats and blind mole‐rats are typical hypoxic model animals as they have some resistance to cancer. This review primarily summarizes the main living environment of hypoxia tolerant small mammals, as well as the changes of phenotype, physiochemical characteristics and gene expression mode of their long‐term living in hypoxia environment.

Transposon-triggered innate immune response confers cancer resistance to the blind mole rat.

Blind mole rats (BMRs) are small rodents, characterized by exceptionally long lifespan (> 21 years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). BMR cells and tissues express very low levels of DNA methyltransferase 1 (DNMT1). Upon cell hyperplasia, the BMR genome DNA loses methylation, resulting in activation of RTEs. Up-regulated RTEs form cytoplasmic RNA/DNA hybrids, which activate cGAS-STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and human. We propose that RTEs were coopted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of innate immune response. RTEs activation is a double-edged sword, serving as a tumor suppressor but in late life contributing to aging via induction of sterile inflammation.

Local Adaptation of Bitter Taste and Ecological Speciation in a Wild Mammal.

Sensory systems are attractive evolutionary models to address how organisms adapt to local environments that can cause ecological speciation. However, tests of these evolutionary models have focused on visual, auditory, and olfactory senses. Here, we show local adaptation of bitter taste receptor genes in two neighboring populations of a wild mammal—the blind mole rat Spalax galili—that show ecological speciation in divergent soil environments. We found that basalt-type bitter receptors showed higher response intensity and sensitivity compared with chalk-type ones using both genetic and cell-based functional analyses. Such functional changes could help animals adapted to basalt soil select plants with less bitterness from diverse local foods, whereas a weaker reception to bitter taste may allow consumption of a greater range of plants for animals inhabiting chalk soil with a scarcity of food supply. Our study shows divergent selection on food resources through local adaptation of bitter receptors, and suggests that taste plays an important yet underappreciated role in speciation.

Comparative Neurology of Circadian Photoreception: The Retinohypothalamic Tract (RHT) in Sighted and Naturally Blind Mammals.

The mammalian eye contains two systems for light perception: an image detecting system constituted primarily of the classical photoreceptors, rods and cones, and a non-image forming system (NIF) constituted of a small group of intrinsically photosensitive retinal ganglion cells driven by melanopsin (mRGCs). The mRGCs receive input from the outer retina and NIF mediates light entrainment of circadian rhythms, masking behavior, light induced inhibition of nocturnal melatonin secretion, pupillary reflex (PLR), and affect the sleep/wake cycle. This review focuses on the mammalian NIF and its anatomy in the eye as well as its neuronal projection to the brain. This pathway is known as the retinohypothalamic tract (RHT). The development and functions of the NIF as well as the knowledge gained from studying gene modified mice is highlighted. Furthermore, the similarities of the NIF between sighted (nocturnal and diurnal rodent species, monkeys, humans) and naturally blind mammals (blind mole rats Spalax ehrenbergi and the Iberian mole, Talpa occidentalis) are discussed in relation to a changing world where increasing exposure to artificial light at night (ALAN) is becoming a challenge for humans and animals in the modern society.

Histological structure of Nannospalax xanthodon cochlea tissue

Because of the growth retardation in the eyes of Nannospalax xanthodon blind mole rat, some genetic and environmental adaptations have occurred in the smelling and hearing systems so that they can communicate efficiently in the galleries underground. This study was aimed to determine the histological and morphometric structure of the unique organization of the cochlea, which plays an important role in hearing in N. xanthodon. After the decalcification process, the cochlear tissue was cut in 5 μm thickness after routine histological procedures. Then these sections stained with Hematoxylin & Eosin and Masson trichrome methods were examined histologically. Besides, the data obtained by taking measurements with the Image J program in the basal, media, and apex regions of the cochlea were evaluated statistically. It was observed that basilar membrane length, tectorial membrane length, stria vascularis thickness, and inner-outer hair cell lengths increased, while Reissner’s membrane length and basilar membrane thickness decreased. These data show that the general histological structure of the blind mole rat cochlea is similar to that of other mammals. By evaluating histomorphological findings, it was concluded that cochlea, which plays a primary role in hearing with the effect of living conditions and genetic structures, develops better in blind mole rats than other living species.

Distinct organization of adaptive immunity in the long-lived rodent Spalax galili.

A balanced immune response is a cornerstone of healthy aging. Here, we uncover distinctive features of the long-lived blind mole-rat (Spalax spp.) adaptive immune system, relative to humans and mice. The T-cell repertoire remains diverse throughout the Spalax lifespan, suggesting a paucity of large long-lived clones of effector-memory T cells. Expression of master transcription factors of T-cell differentiation, as well as checkpoint and cytotoxicity genes, remains low as Spalax ages. The thymus shrinks as in mice and humans, while interleukin-7 and interleukin-7 receptor expression remains high, potentially reflecting the sustained homeostasis of naive T cells. With aging, immunoglobulin hypermutation level does not increase and the immunoglobulin-M repertoire remains diverse, suggesting shorter B-cell memory and sustained homeostasis of innate-like B cells. The Spalax adaptive immune system thus appears biased towards sustained functional and receptor diversity over specialized, long-lived effector-memory clones-a unique organizational strategy that potentially underlies this animal's extraordinary longevity and healthy aging.

Comparative analysis of SARS-CoV-2 and its receptor ACE2 with evolutionarily related coronaviruses

The pandemic COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is spreading very rapidly worldwide. To date, the origin and intermediate hosts of SARS-CoV-2 remain unclear. In this study, we conducted comparative analysis among SARS-CoV-2 and non-SARS-CoV-2 coronavirus strains to elucidate their phylogenetic relationships. We found: 1, the SARS-CoV-2 strains analyzed could be divided into 3 clades with regional aggregation; 2, the non-SARS-CoV-2 common coronaviruses that infect humans or other organisms to cause respiratory syndrome and epizootic catarrhal gastroenteritis could also be divided into 3 clades; 3, the hosts of the common coronaviruses closest to SARS-CoV-2 were Apodemus chevrieri (a rodent), Delphinapterus leucas (beluga whale), Hypsugo savii (bat) , Camelus bactrianus (camel) and Mustela vison (mink); and 4, the gene sequences of the receptor ACE2 from different hosts could also be divided into 3 clades. The ACE2 gene sequences closest to that of humans in evolution include those from Nannospalax galili (Upper Galilee mountains blind mole rat), Phyllostomus discolor (pale spear-nosed bat), Mus musculus (house mouse), Delphinapterus leucas (beluga whale), and Catharus ustulatus (Swainson's thrush). We conclude that SARS-CoV-2 may have evolved from a distant common ancestor with the common coronaviruses but not a branch of any of them, implying that the prevalent pandemic COVID-19 agent SARS-CoV-2 may have existed in a yet to be identified primary host for a long time.

Histopathological Analysis of The Eye And Optic Nerve Structure In The Blind Mole Rat

Objective: Blind mole rats (Nannospalax xanthodon Nehring, 1898) are subterranean mammals that are well-known for their high tolerance to hypoxia and resistance to cancer. Due to their unusual habitat, these animals have developed several adaptations during their evolution. Therefore, this study aimed to identify possible structural differences in Nannospalax visual system in comparison to other mammals that might have arisen as a result of adaptation to underground life.
 Method: Six blind mole rats were used in the study. No procedure was performed on the rats. After the animals were anesthetized with ether, their eyes and optic nerves were removed. For this purpose, pseudo-eyes and optic nerves were harvested and fixed in 10% formaldehyde for a week. Tissues were embedded into paraffin and blocked via routine histological procedures. Five micrometer sections in thickness were taken and stained with Hematoxylin & Eosin (H&E) and Cresyl Violet.
 Results: Histopathological analysis of the eye revealed the presence of cornea, retina, sclera, iris, zonula adherens, lacrimal gland and ducts, fatty tissue, muscle layer and the vascular structures. No pathology was observed of optic nerve.
 Conclusions: We found that the visual system of N. xanthodon share some similarities with other blind mole rat species from Israel, while some histological properties were defined by our study for the first time in the literature.

Microbiome and Longevity: High Abundance of Longevity-Linked Muribaculaceae in the Gut of the Long-Living Rodent Spalax leucodon.

With a world population living longer as well as marked disparities in life expectancy, understanding the determinants of longevity is one of the priority research agendas in 21st century life sciences. To this end, the blind mole-rat (Spalax leucodon), a subterranean mammalian, has emerged as an exceptional model organism due to its astonishing features such as remarkable longevity, hypoxia and hypercapnia tolerance, and cancer resistance. The microbiome has been found to be a vital parameter for cellular physiology and it is safe to assume that it has an impact on life expectancy. Although the unique characteristics of Spalax make it an ideal experimental model for longevity research, there is limited knowledge of the bacterial composition of Spalax microbiome, which limits its in-depth utilization. In this study, using 16S rRNA amplicon sequencing, we report the gut and skin bacterial structure of Spalax for the first time. The diversity between fecal and skin samples was manifested in the distant clustering, as revealed by beta diversity analysis. Importantly, the longevity-linked Muribaculaceae bacterial family was found to be the dominating bacterial taxa in Spalax fecal samples. These new findings contribute toward further development of Spalax as a model for longevity research and potential linkages between microbiome composition and longevity.

Recapitulating Evolutionary Divergence in a Single Cis-Regulatory Element Is Sufficient to Cause Expression Changes of the Lens Gene Tdrd7.

Mutations in cis-regulatory elements play important roles for phenotypic changes during evolution. Eye degeneration in the blind mole rat (BMR; Nannospalax galili) and other subterranean mammals is significantly associated with widespread divergence of eye regulatory elements, but the effect of these regulatory mutations on eye development and function has not been explored. Here, we investigate the effect of mutations observed in the BMR sequence of a conserved noncoding element upstream of Tdrd7, a pleiotropic gene required for lens development and spermatogenesis. We first show that this conserved element is a transcriptional repressor in lens cells and that the BMR sequence partially lost repressor activity. Next, we recapitulated evolutionary changes in this element by precisely replacing the endogenous regulatory element in a mouse line by the orthologous BMR sequence with CRISPR–Cas9. Strikingly, this repressor replacement caused a more than 2-fold upregulation of Tdrd7 in the developing lens; however, increased mRNA level does not result in a corresponding increase in TDRD7 protein nor an obvious lens phenotype, possibly explained by buffering at the posttranscriptional level. Our results are consistent with eye degeneration in subterranean mammals having a polygenic basis where many small-effect mutations in different eye-regulatory elements collectively contribute to phenotypic differences.

Comparative analysis of the different regions of skin tissue in Nannospalax xanthodon

Blind mole rats (Nannospalax xanthodon Palmer, 1903) are subterranean mammals that are well-known for their high tolerance to hypoxia and resistance to cancer. Due to their unusual habitat, these animals have developed several adaptations during their evolution. Therefore, this study aimed to identify possible structural differences between different regions of the skin in Nannospalax as well as to characterize the histological organization of a specialized skin patch namely scrub sensory organ that have possibly arisen as a result of adaptation to underground life. Skin from the neck, nasal pad and the scrub sensory organ was harvested from wildtype blind mole rats and fixed in 10% formaldehyde. Tissues were embedded into paraffin and blocked via routine histological procedures. 5-micron sections were taken and stained with Hematoxylin & Eosin and Cresyl Violet. Histopathological analysis of the skin revealed that the nasal pad and the scrub sensory organ were significantly thicker compared to the neck skin. Skin epithelia was structurally normal, although it was thicker in the neck skin in comparison to others. We observed structures that are similar to pyramidal cells in the scrub sensory organ. In conclusion, we defined some histological properties of the scrub sensory organ in Nannospalax xanthodon for the first time in the literature. Specifically, the detection of structures that are similar to pyramidal cells is significant. These results indicate structural differences between different skin regions and suggest a role for the scrub sensory organ in somatosensation.