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.

中文翻译：

---

裸鼹鼠，一种带有载脂蛋白 A-I 二聚体的啮齿动物

多种啮齿动物已被用作血浆脂质和脂蛋白代谢研究的实验动物。这些研究包括了解载脂蛋白 A-I（HDL 表面的主要蛋白质）的功能作用。审查啮齿动物apoA-I基因条目的基因组数据库，发现裸鼹鼠（Heterocephalus glaber) 基因编码的蛋白质在残基 28 处具有半胱氨酸。 以前，已经报道了两个案例，其中人类杂合子在残基 173 (apoA-I Milano) 或 151 (apoA-I Paris) 处具有半胱氨酸的 apoA-I。有趣的是，尽管 HDL 水平低且血浆三酰甘油水平适度升高，但两组都没有心血管疾病的证据。此外，半胱氨酸的存在使 apoA-I 能够形成同源二聚体和异源二聚体。在本报告之前，尚未发现其他哺乳动物的 apoA-I 序列中含有半胱氨酸。此外，编码的裸鼹鼠蛋白在所有其他哺乳动物中保守的位点具有不同的氨基酸。这些差异导致裸鼹鼠 apoA-I 具有意外的中性 pI 值，而其他哺乳动物的 apoA-I 具有负 pI 值。为了验证这些序列差异并确定 C28 的 N 末端位置是否阻止了二聚体的形成，我们对 apoA-I 和其他与 HDL 相关的蛋白质进行了质谱分析。与基因组数据一致，我们的分析证实了 C28 的存在和同源二聚体的形成。血浆脂质分析令人惊讶地揭示了与人类杂合子相似的特征。