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1. Naked Mole‐Rat, a Rodent with an Apolipoprotein A‐I Dimer

   https://doi.org/10.1002/lipd.12286  

   Puppione, Don L. ; Tran, Denise P. ; Zenaidee, Muhammad A. ; Charugundla, Sarada ; Whitelegge, Julian P. ; Buffenstein, Rochelle ( December 2020 , Lipids)

   A variety of rodents have been used as experimental animals in metabolic studies of plasma lipids and lipoproteins. These studies have included understanding the functional role of apolipoprotein A‐I, the major protein on the surface of HDL. Reviewing the genomic database for entries for rodentapoA‐Igenes, it was discovered that the naked mole‐rat (Heterocephalus glaber) gene encoded a protein with a cysteine at residue 28. Previously, two cases have been reported in which human heterozygotes had apoA‐I with cysteine at residues 173 (apoA‐I Milano) or at 151 (apoA‐I Paris). Interestingly, both groups, in spite of having low levels of HDL and moderately elevated plasma triacylglycerols, had no evidence of cardiovascular disease. Moreover, the presence of the cysteine enabled the apoA‐I to form both homodimers and heterodimers. Prior to this report, no other mammalian apoA‐I has been found with a cysteine in its sequence. In addition, the encoded naked mole‐rat protein had different amino acids at sites that were conserved in all other mammals. These differences resulted in naked mole‐rat apoA‐I having an unexpected neutral pI value, whereas other mammalian apoA‐I have negative pI values. To verify these sequence differences and to determine if the N‐terminal location of C28 precluded dimer formation, we conducted mass spectrometry analyses of apoA‐I and other proteins associated with HDL. Consistent with the genomic data, our analyses confirmed the presence of C28 and the formation of a homodimer. Analysis of plasma lipids surprisingly revealed a profile similar to the human heterozygotes.

    

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2. Naked Mole‐Rats: Blind, Naked, and Feeling No Pain

   https://doi.org/10.1002/ar.23996  

   Browe, Brigitte M. ; Vice, Emily N. ; Park, Thomas J. ( November 2018 , The Anatomical Record)

   Around the world and across taxa, subterranean mammals show remarkable convergent evolution in morphology (e.g., reduced external ears, small eyes, shortened limbs and tails). This is true of sensory systems as well (e.g., loss of object vision and high frequency hearing). The naked mole‐rat (Heterocephalus glaber) displays these typical subterranean features, but also has unusual characteristics even among subterranean mammals. Naked mole‐rats are cold‐blooded, completely furless, very long‐lived (> 30 years), and eusocial (like termites). They also live in large colonies, which is very unusual for subterraneans. Their cortical organization has reduced area for visual processing, utilizing 30% more cortex for tactile processing. They are extremely tolerant to oxygen deprivation, and can recover from 18 min of anoxia. Their pain pathway is reduced and they feel no pain from acidosis. They are the only rodent tested to date whose pheromone‐detecting vomeronasal organ shows no postnatal growth. These features may be a result of this species' “extreme subterranean lifestyle” that combines living underground and living in large colonies. Many respiring animals cramped together in unventilated burrows elevates CO₂levels, high enough to cause acidosis pain, and depletes O₂concentrations low enough to kill other mammals. The naked mole‐rat may be an extreme model of adaptation to subterranean life and provides insights into the complex interplay of evolutionary adaptations to the constraints of subterranean living. Anat Rec, 2018. © 2018 American Association for Anatomy.

    

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3. Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro

   https://doi.org/10.18632/aging.202138  

   Frankel, Daniel ; Davies, Matthew ; Bhushan, Bharat ; Kulaberoglu, Yavuz ; Urriola-Munoz, Paulina ; Bertrand-Michel, Justine ; Pergande, Melissa R. ; Smith, Andrew A. ; Preet, Swapan ; Park, Thomas J. ; et al ( October 2020 , Aging)

   null (Ed.)

   Naked mole-rats are extraordinarily long-lived rodents that offer unique opportunities to study the molecular origins of age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta (Aβ) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against Aβ neurotoxicity. Here we examine the composition, phase behaviour, and Aβ interactions of naked mole-rat brain lipids. Relative to mouse, naked mole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorter chain lengths. Proteins associated with the metabolism of ceramides, sphingomyelins and sphingosine-1-phosphate receptor 1 were also found to be decreased in naked mole-rat brain lysates. Correspondingly, we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, with the liquid ordered phase extending to 80% of the supported lipid bilayer. These observations are consistent with the ‘membrane pacemaker’ hypothesis of ageing, according to which long-living species have lipid membranes particularly resistant to oxidative damage. We also found that exposure to Aβ disrupts naked mole-rat brain lipid membranes significantly, breaking the membrane into pieces while mouse brain derived lipids remain largely intact upon Aβ exposure. 

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4. Altered cochlear innervation in developing and mature naked and Damaraland mole rats

   https://doi.org/10.1002/cne.24682  

   Barone, Catherine M. ; Douma, Sytse ; Reijntjes, Daniël O. J. ; Browe, Brigitte M. ; Köppl, Christine ; Klump, Georg ; Park, Thomas J. ; Pyott, Sonja J. ( March 2019 , Journal of Comparative Neurology)

   Compared to many other rodent species, naked mole rats (Heterocephalus glaber) have elevated auditory thresholds, poor frequency selectivity, and limited ability to localize sound. Because the cochlea is responsible for encoding and relaying auditory signals to the brain, we used immunofluorescence and quantitative image analysis to examine cochlear innervation in mature and developing naked mole rats compared to mice (Mus musculus), gerbils (Meriones unguiculatus), and Damaraland mole rats (Fukomys damarensis), another subterranean rodent. In comparison to mice and gerbils, we observed alterations in afferent and efferent innervation as well as their patterns of developmental refinement in naked and Damaraland mole rats. These alterations were, however, not always shared similarly between naked and Damaraland mole rats. Most conspicuously, in both naked and Damaraland mole rats, inner hair cell (IHC) afferent ribbon density was reduced, whereas outer hair cell afferent ribbon density was increased. Naked and Damaraland mole rats also showed reduced lateral and medial efferent terminal density. Developmentally, naked mole rats showed reduced and prolonged postnatal reorganization of afferent and efferent innervation. Damaraland mole rats showed no evidence of postnatal reorganization. Differences in cochlear innervation specifically between the two subterranean rodents and more broadly among rodents provides insight into the cochlear mechanisms that enhance frequency sensitivity and sound localization, maturation of the auditory system, and the evolutionary adaptations occurring in response to subterranean environments.

    

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5. Is the Mole Rat Vomeronasal Organ Functional?

   https://doi.org/10.1002/ar.24060  

   Dennis, John C. ; Stilwell, Natalie K. ; Smith, Timothy D. ; Park, Thomas J. ; Bhatnagar, Kunwar P. ; Morrison, Edward E. ( January 2019 , The Anatomical Record)

   The colonial naked mole ratHeterocephalus glaberis a subterranean, eusocial rodent. TheH. glabervomeronasal organ neuroepithelium (VNE) displays little postnatal growth. However, the VNE remains neuronal in contrast to some mammals that possess nonfunctional vomeronasal organ remnants, for example, catarrhine primates and some bats. Here, we describe the vomeronasal organ (VNO) microanatomy in the naked mole rat and we make preliminary observations to determine ifH. glabershares its minimal postnatal VNE growth with other African mole rats. We also determine the immunoreactivity to the mitotic marker Ki67, growth‐associated protein 43 (GAP43), and olfactory marker protein (OMP) in six adult and three subadultH. glaberindividuals. VNE volume measurements on a small sample ofCryptomys hottentotusandFukomys damarensisindicate that the VNE of those African mole rat species are also likely to be growth‐deficient. Ki67(+) cells show that the sensory epithelium is mitotically active. GAP43 labelling indicates neurogenesis and OMP(+) cells are present though less numerous compared to GAP43(+) cells. In this respect, the VNO ofH. glaberdoes not appear vestigial. The African mole rat VNE may be unusually variable, perhaps reflecting reduced selection pressure on the vomeronasal system. If so, African mole rats may provide a useful genetic model for understanding the morphological variability observed in the mammalian VNO. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 303:318–329, 2020. © 2019 American Association for Anatomy

    

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