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

Abstract

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 rodent apoA-I genes, 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.Keywords apoA-I Á apoE Á Homodimer Á hypoHDL Á Mass spectrometry Á Rodentia

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Ectopic cervical thymi and no thymic involution until midlife in naked mole-rats

“…NMRs show a very low incidence of cancer (Buffenstein, 2008, Delaney et al, 2013, Delaney et al, 2016. NMRs produce abundant high molecular weight hyaluronic acid (HMW-HA) responsible for their resistance to solid tumors (Tian et al, 2013a, Tian et al, 2015 and feature a serum metabolome resembling calorically restricted mice (Lewis et al, 2018, Puppione et al, 2021. Thus, NMRs present a unique model to study the mechanisms of healthy longevity (Edrey et al, 2011.…”