CHARACTERIZATION OF METALLOTHIONEIN-I-TRANSGENIC MICE
CHARACTERIZATION OF METALLOTHIONEIN-I-TRANSGENIC MICE
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DOI：
10.1006/taap.1995.1155
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发表时间：
1995-08-01
影响因子：
3.8
通讯作者：
KLAASSEN, CD
中科院分区：
文献类型：
--
作者：
ISZARD, MB;LIU, J;KLAASSEN, CD
对一种金属硫蛋白- 1转基因小鼠品系（MT-TG）进行了表征，以确定它们是否适合研究该蛋白的功能。从视觉上看，MT- tg小鼠与非转基因的同卵小鼠没有区别，但胰腺、肝脏和胃的MT蛋白基础水平比对照小鼠高10- 20倍，其他器官（肾脏、肠道、子宫、睾丸、脾脏、心脏和肺）的MT蛋白水平比对照小鼠高2- 6倍，这是通过Cd/血红蛋白测定的。MT-TG小鼠肝脏锌含量比对照组高50%，胰腺锌含量比对照组高300%。有趣的是，雌性MT- tg小鼠肝脏中的MT水平比雄性小鼠高4- 5倍。为了确定MT诱导剂是否能进一步增加MT，对照小鼠和MT- tg小鼠分别给予Zn （200 mu mol/kg）、Cd （20 mu mol/kg）或马来酸二乙酯（DEM, 5 mmol/kg），并于24小时后测定组织MT浓度。MT- tg小鼠对MT诱导剂的反应方式与对照小鼠相似。MT-TG小鼠肝脏抗氧化成分（谷胱甘肽（GSH）、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽s -转移酶、超氧化物歧化酶、DT-diaphorase和过氧化氢酶）与对照组无显著差异。MT-TG小鼠细胞色素P450酶（total P450, b(5)， NADPH细胞色素c还原酶）正常。通过乙氧基和己氧基间苯二酚o脱烷基和氯唑唑酮i-羟基化测定，MT-TG小鼠CYP1A、CYP2B和CYP2E酶活性也与对照组相似。因此，MT- tg小鼠似乎是研究MT功能的良好模型。(C) 1995学术出版社，Inc.。
A metallothionein-I-transgenic mouse strain (MT-TG) was characterized to determine whether they would be suitable to study the functions of this protein. MT-TG mice were visually indistinguishable from nontransgenic littermate controls, but had 10- to 20-fold higher basal levels of MT protein in pancreas, liver, and stomach, as well as 2- to 6-fold higher MT protein levels in other organs (kidney, intestine, uterus, testes, spleen, heart, and lung) than control mice, as determined by the Cd/hemoglobin assay. The MT-TG mice had 50% more Zn in liver and 300% more Zn in pancreas than control mice. Interestingly, female MT-TG mice have 4- to 5-fold higher MT levels in liver than those of males. To determine whether MT can be further increased by well-known MT inducers, control and MT-TG mice were given Zn (200 mu mol/kg), Cd (20 mu mol/kg), or diethyl maleate (DEM, 5 mmol/kg), and tissue MT concentrations were measured 24 hr later. MT-TG mice responded to MT inducers in a manner similar to control mice. The hepatic antioxidant components (glutathione (GSH), GSH-peroxidase, GSH-reductase, GSH S-transferase, superoxide dismutase, DT-diaphorase, and catalase) of MT-TG mice were not different from those of controls. The cytochrome P450 enzymes (total P450, b(5), NADPH cytochrome c reductase) were normal in these MT-TG mice. The activities of CYP1A, CYP2B, and CYP2E enzymes in MT-TG mice were also similar to those of controls, as determined by ethoxy- and pentoxyresorufin O-dealkylation and chlorzoxazone fi-hydroxylation. Thus, MT-TG mice appear to be a good model for studying functions of MT. (C) 1995 Academic Press, Inc.