Autosomal dominant familial hypercholesterolemia (ADH; MIM#143890) is one of the most common monogenic disorders characterized by elevated circulatory LDL cholesterol. Initial studies in humans with ADH identified a potential relationship with variants of the gene encoding signal transducing adaptor family member protein 1 (STAP1; MIM#604298). However, subsequent studies have been contradictory. In this study, mice lacking global Stap1 expression (Stap1−/−) were characterized under standard chow and a 42% kcal western diet (WD). Mice were studied for changes in different metabolic parameters before and after a 16-week WD regime. Growth curves, body fats, circulatory lipids, parameters of glucose homeostasis, and liver architecture were studied for comparisons. Surprisingly, Stap1−/− mice fed the 16-week WD demonstrated no marked differences in any of the metabolic parameters compared to Stap1+/+ mice. Furthermore, hepatic architecture and cholesterol content in FPLC-isolated lipoprotein fractions also remained comparable to wild-type mice. These results strongly suggest that STAP1 does not alter lipid levels, that a western diet did not exacerbate a lipid disorder in Stap1 deficient mice and support the contention that it is not causative for hyperlipidemia in ADH patients. These results support other published studies also questioning the role of this locus in human hypercholesterolemia.

中文翻译：

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缺乏全局Stap1表达的小鼠不会表现出高胆固醇血症

常染色体显性家族性高胆固醇血症（ADH; MIM＃143890）是最常见的单基因疾病之一，其特征是循环LDL胆固醇升高。在具有ADH的人类中的初步研究确定了与编码信号转导衔接子家族成员蛋白1（STAP1; MIM＃604298）的基因的变体之间的潜在关系。但是，随后的研究是矛盾的。在这项研究中，以标准食物和42％大卡的西方饮食（WD）对缺乏全局Stap1表达（Stap1-/-）的小鼠进行了表征。研究小鼠在16周WD治疗前后不同代谢参数的变化。比较了生长曲线，人体脂肪，循环脂质，葡萄糖稳态参数和肝脏结构。出奇，与Stap1 + / +小鼠相比，喂食16周WD的Stap1-/-小鼠在任何代谢参数上均无明显差异。此外，FPLC分离的脂蛋白组分中的肝结构和胆固醇含量也仍然与野生型小鼠相当。这些结果强烈表明，STAP1不会改变血脂水平，西方饮食不会加剧Stap1缺陷小鼠的血脂紊乱，并支持它对ADH患者高脂血症无病的论点。这些结果支持其他已发表的研究，也质疑了该基因座在人类高胆固醇血症中的作用。这些结果强烈表明，STAP1不会改变血脂水平，西方饮食不会加剧Stap1缺陷小鼠的血脂紊乱，并支持它对ADH患者高脂血症无病的论点。这些结果支持其他已发表的研究，也质疑了该基因座在人类高胆固醇血症中的作用。这些结果强烈表明，STAP1不会改变血脂水平，西方饮食不会加剧Stap1缺陷小鼠的血脂紊乱，并支持它对ADH患者高脂血症无病的论点。这些结果支持其他已发表的研究，也质疑了该基因座在人类高胆固醇血症中的作用。