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大鼠中枢神经系统表达阿尔茨海默病淀粉样前体蛋白APP695,但不表达APP677(L-APP形式)。

The rat central nervous system expresses Alzheimer's amyloid precursor protein APP695, but not APP677 (L-APP form).

作者信息

Ohgami T, Kitamoto T, Tateishi J

机构信息

Department of Neuropathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

J Neurochem. 1993 Oct;61(4):1553-6. doi: 10.1111/j.1471-4159.1993.tb13655.x.

Abstract

A novel splicing form of beta A4 amyloid precursor protein (APP) lacking exon 15, corresponding to 18 residues, was first reported in leukocytes and then in ubiquitous organs. To determine which APP molecules (APP695, APP751, or APP770) either with (N-APP) or without (L-APP; leukocyte-derived APP) exon 15 were expressed in various organs, we investigated the alternative splicing at exon 15 in the rat brain, kidney, heart, and testis by a PCR analysis of reverse-transcribed RNA and Southern blot analysis. Regarding APP695 without exons 7 and 8, L-APP was either seldom or never expressed in the brain, whereas both N- and L-APP were expressed in other organs. On the other hand, regarding APP751/770 containing exon 7, which codes for the Kunitz-type serine protease inhibitor domain, both N- and L-APP were expressed in all the organs examined, including the brain. These results suggest that a particular alternative regulation system related to exon 15 might be present in only APP695 of the brain and influence the proteolytic processing of APP.

摘要

一种缺少第15外显子(对应18个残基)的新型β淀粉样前体蛋白(APP)剪接形式首先在白细胞中被报道,随后在全身各器官中被发现。为了确定在各器官中表达的是带有(N-APP)还是不带有(L-APP;白细胞衍生APP)第15外显子的哪些APP分子(APP695、APP751或APP770),我们通过对逆转录RNA进行PCR分析和Southern印迹分析,研究了大鼠脑、肾、心脏和睾丸中第15外显子的可变剪接情况。对于缺少第7和第8外显子的APP695,L-APP在脑中很少表达或从不表达,而N-APP和L-APP在其他器官中均有表达。另一方面,对于含有编码Kunitz型丝氨酸蛋白酶抑制剂结构域的第7外显子的APP751/770,N-APP和L-APP在包括脑在内的所有检测器官中均有表达。这些结果表明,仅在脑的APP695中可能存在与第15外显子相关的特定可变调控系统,并影响APP的蛋白水解加工过程。

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