Tsushima Hiromi, Yamada Kazuyo, Miyazawa Daisuke, Ohkubo Takeshi, Michikawa Makoto, Abe-Dohmae Sumiko
Laboratory of Pharmacology, College of Pharmacy, Kinjo Gakuin University.
Laboratory of Biochemistry, College of Pharmacy, Kinjo Gakuin University.
Biol Pharm Bull. 2021;44(12):1851-1859. doi: 10.1248/bpb.b21-00543.
The physical characteristics and behavior of the ATP-binding cassette (ABC) A1, A7, and apolipoprotein (apo) E knockout (KO) mice with lipid transport dysfunction were investigated. These KO mice exhibited adequate growth, and their body masses increased steadily. No remarkable changes were observed in their blood pressure and heart rate. However, there was a slight increase in the heart rate of the ABCA7 KO mice compared with that of the wild-type (WT) mice. ABCA1 and apoE KO mice showed hypo- and hyper-cholesterol concentrations in the plasma, respectively. With regard to the cerebrum, however, the weight of the ABCA1 KO mice was lighter than those of the other genotypes. Furthermore, the cholesterol, triglyceride and phospholipid concentrations, and fatty acid composition were generally similar. Compared with the WT mice, ABCA1 KO mice stayed for a shorter time in the closed arm of the elevated plus maze, and performed worse in the initial stage of the Morris water maze. To thermal stimuli, the ABCA1 and apoE KO mice showed hyper- and hypo-sensitivities, respectively. Only the response of the ABCA1 KO mice was significantly inhibited by pretreatment with indomethacin. A low concentration of the prostaglandin E metabolites was detected in the plasma of the ABCA1 KO mice. Thus, ABCA1 is thought to play a specific role in the neural function.
对具有脂质转运功能障碍的三磷酸腺苷结合盒(ABC)A1、A7和载脂蛋白(apo)E基因敲除(KO)小鼠的身体特征和行为进行了研究。这些基因敲除小鼠生长正常,体重稳步增加。它们的血压和心率未观察到明显变化。然而,与野生型(WT)小鼠相比,ABCA7基因敲除小鼠的心率略有增加。ABCA1和apoE基因敲除小鼠的血浆中分别出现低胆固醇和高胆固醇浓度。然而,就大脑而言,ABCA1基因敲除小鼠的脑重量比其他基因型的小鼠轻。此外,胆固醇、甘油三酯和磷脂浓度以及脂肪酸组成总体上相似。与野生型小鼠相比,ABCA1基因敲除小鼠在高架十字迷宫封闭臂中的停留时间较短,在莫里斯水迷宫的初始阶段表现较差。对于热刺激,ABCA1和apoE基因敲除小鼠分别表现出高敏感性和低敏感性。只有ABCA1基因敲除小鼠的反应被吲哚美辛预处理显著抑制。在ABCA1基因敲除小鼠的血浆中检测到低浓度的前列腺素E代谢产物。因此,ABCA1被认为在神经功能中起特定作用。