公开(公告)号：WO1996010074A1

公开(公告)日：1996-04-04

申请号：PCT/US1995013051

申请日：1995-09-27

Applicant: VANDERBILT UNIVERSITY

Inventor： VANDERBILT UNIVERSITY ,  CAPDEVILLA, Jorge ,  MAKITA, Keiko ,  KARARA, Armando

IPC: C12N05/00

CPC classification number: C12N9/0077 ,  A61K49/0004

Abstract: The invention provides an isolated nucleic acid encoding the rat P450 2C11 arachidonic acid epoxygenase, or a human homologue thereof, having a mutation associated with salt induced hypertension. Also provided is an isolated cell line expressing the epoxygenase encoded by the emutated nucleic acid, and a non-human transgenic animal having a germ line insertion of the mutated nucleic acid. Also provided is a method of screening a compound for efficacy in treating salt induced hypertension comprising administering the compound to such a non-human transgenic animal, and detecting an improvement in the animal's hypertension. The invention also provides a method of screening a human subject for a genetic predisposition to salt induced hypertension comprising detecting a mutation in a human homologue of a rat P450 2C11 arachidonic acid epoxygenase gene which affects normal epoxygenase activity. Also provided is a method of treating salt induced hypertension in a human subject associated with a genetic mutation in a human homologue of the rat P450 2C11 arachidonic acid epoxygenase gene, comprising administering to the subject a functional metabolite, or analogue thereof, produced by the human homologue of the rat P450 2C11 arachidonic acid epoxygenase. Also provided is an isolated mutated rat P450 2C11 arachidonic acid epoxygenase, or a human homologue thereof, having a mutation associated with salt induced hypertension.

Abstract translation: 本发明提供编码具有与盐诱导的高血压相关的突变的大鼠P450 2C11花生四烯酸环氧化酶或其人类同源物的分离的核酸。 还提供了表达由引发的核酸编码的环氧化酶的分离的细胞系和具有突变核酸的种系插入的非人转基因动物。 还提供了筛选化合物以治疗盐诱导的高血压的功效的方法，包括给予这种非人转基因动物的化合物，并检测动物的高血压的改善。 本发明还提供了筛选人类受试者对盐诱导的高血压的遗传易感性的方法，包括检测影响正常环氧化酶活性的大鼠P450 2C11花生四烯酸环氧化酶基因的人类同源物中的突变。 还提供了一种治疗与大鼠P450 2C11花生四烯酸环氧化酶基因的人同源物中的遗传突变相关的人类受试者的盐诱导的高血压的方法，包括向受试者施用由人产生的功能性代谢物或其类似物 大鼠P450 2C11花生四烯酸环氧化酶的同系物。 还提供了具有与盐诱发的高血压相关的突变的分离的突变大鼠P450 2C11花生四烯酸环氧化酶或其人类同源物。