Yamamoto T, Bishop R W, Brown M S, Goldstein J L, Russell D W
Science. 1986 Jun 6;232(4755):1230-7. doi: 10.1126/science.3010466.
The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal with familial hypercholesterolemia, produces a mutant receptor for plasma low-density lipoprotein (LDL) that is not transported to the cell surface at a normal rate. Cloning and sequencing of complementary DNA's from normal and WHHL rabbits, shows that this defect arises from an in-frame deletion of 12 nucleotides that eliminates four amino acids from the cysteine-rich ligand binding domain of the LDL receptor. A similar mutation, detected by S1 nuclease mapping of LDL receptor messenger RNA, occurred in a patient with familial hypercholesterolemia whose receptor also fails to be transported to the cell surface. These findings suggest that animal cells may have fail-safe mechanisms that prevent the surface expression of improperly folded proteins with unpaired or improperly bonded cysteine residues.
渡边遗传性高脂血症（WHHL）兔是一种患有家族性高胆固醇血症的动物，它产生一种血浆低密度脂蛋白（LDL）的突变受体，该受体不能以正常速率转运到细胞表面。对正常兔和WHHL兔的互补DNA进行克隆和测序表明，这种缺陷是由于12个核苷酸的读框内缺失所致，该缺失从LDL受体富含半胱氨酸的配体结合域中消除了4个氨基酸。通过对LDL受体信使RNA进行S1核酸酶图谱分析检测到，一名家族性高胆固醇血症患者也发生了类似突变，其受体同样无法转运到细胞表面。这些发现表明，动物细胞可能具有故障安全机制，可防止具有未配对或结合不当的半胱氨酸残基的错误折叠蛋白在细胞表面表达。
