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在用9-乙基腺嘌呤处理的次黄嘌呤磷酸核糖转移酶(HPRT)缺陷小鼠中未发现自伤行为。

No self-injurious behavior was found in HPRT-deficient mice treated with 9-ethyladenine.

作者信息

Edamura K, Sasai H

机构信息

Life Science Research Laboratory, Japan Tobacco Inc., Yokohama, Kanagawa.

出版信息

Pharmacol Biochem Behav. 1998 Oct;61(2):175-9. doi: 10.1016/s0091-3057(98)00095-1.

Abstract

It has been reported that 9-ethyladenine (9-EA) is an efficient inhibitor of APRT (adenine phosphoribosyltransferase) and that its administration causes self-injurious behavior (Lesch-Nyhan Syndrome-like symptoms) in HPRT (hypoxanthine-guanine phosphoribosyltransferase)-deficient mice. In contrast, we found neither any self-injurious behavior (SIB), such as visible injury or hair loss, nor any apparent decrease in APRT activity in HPRT-deficient mice treated with 9-EA. We also found that 9-EA has little irreversible or competitive inhibitory effect on APRT in vitro, even at a concentration of 10(-2) M. In light of the negative finding of SIB in APRT/HPRT double-deficient mice, it seems unlikely that SIB in HPRT-deficient mice is caused by lowered APRT activity. It is concluded that 9-EA is not a sufficient APRT inhibitor and cannot be used in experiments that mimic lowered APRT status in an animal model.

摘要

据报道,9-乙基腺嘌呤(9-EA)是腺嘌呤磷酸核糖转移酶(APRT)的有效抑制剂,给次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HPRT)缺陷小鼠施用9-EA会导致自伤行为(莱施-奈恩综合征样症状)。相比之下,我们在用9-EA处理的HPRT缺陷小鼠中既未发现任何自伤行为(SIB),如可见损伤或毛发脱落,也未发现APRT活性有任何明显降低。我们还发现,即使在浓度为10(-2)M时,9-EA在体外对APRT几乎没有不可逆或竞争性抑制作用。鉴于在APRT/HPRT双缺陷小鼠中未发现SIB这一阴性结果,HPRT缺陷小鼠中的SIB似乎不太可能是由APRT活性降低所致。结论是,9-EA不是一种有效的APRT抑制剂,不能用于模拟动物模型中APRT状态降低的实验。

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