Generation of genetically-altered mice producing very low levels of coagulation factor VII
Generation of genetically-altered mice producing very low levels of coagulation factor VII
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DOI：
10.1160/th05-05-0337
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发表时间：
2005-09-01
影响因子：
6.7
通讯作者：
Castellino, FJ
中科院分区：
文献类型：
--
作者：
Rosen, ED;Xu, HF;Castellino, FJ
早期研究表明，完全靶向缺失凝血因子VII基因（FVII-/-）的小鼠在围产期死亡，从而排除了对完全缺乏FVII基因的成年动物的研究。因此，在四环素反式激活因子（tTA）启动子的控制下，通过用其相应的cDNA靶向替换野生型（WT）鼠FVII基因，开发了产生极低水平FVII的小鼠。当回交到C57 B1/6品系中时，含有两个FVII缺陷、减少的、基因改变的小鼠、靶向基因置换放置的FVIII等位基因（FVIItTA/tTA）的未攻击小鼠产生约0.7%的WT FVII水平，但仍存活至成年，尽管在年轻成年年龄显示严重下调的总体凝血酶产生和自发发展的心脏纤维化。这种基因改变的小鼠系提供了一种极好的动物模型，用于研究未受攻击的小鼠和经受各种实验攻击的小鼠中严重FVII缺乏的后果。
It has been shown earlier that mice with a total targeted deletion of the factorVIIgene (FVII-/- ) die perinatally, thereby precluding study of adult animals with this total deficiency. Consequently, mice producing very low levels of FVII were developed by targeted replacement of the wild-type (WT) murine FVII gene with its corresponding cDNA, under control of the tetracycline transactivator (tTA) promoter. When backcrossed into the C57Bl/6 strain, unchallenged mice containing two FVII deficiency, reduced , gene-altered mice, targeted gene replacement placed FVIII alleles (FVIItTA/tTA) produce approximately 0.7% of WT FVII levels, but yet live to adulthood despite displaying severely downregulated overall thrombin production and spontaneously developing cardiac fibrosis at a young adult age. This genetically-altered mouse line provides an excellent animal model to study consequences of a severe FVII deficiency in unchallenged mice and in mice subjected to a variety of experimental challenges.