首页> 外国专利> Method for making a genetically modified mouse with an inducible ACVR1 mutation that causes ectopic bone formation

Method for making a genetically modified mouse with an inducible ACVR1 mutation that causes ectopic bone formation

机译：具有导致异位骨形成的可诱导ACVR1突变的转基因小鼠的制备方法

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摘要

A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.

机译：提供了一种遗传修饰的小鼠，其包含条件性Acvr1等位基因，该条件等位基因包含突变的外显子，该外显子在诱导后转化为突变型外显子表型，其中所述突变型外显子表型包括异位骨形成。提供了在反义方向上包含突变Acvr1外显子5的小鼠，其侧翼为位点特异性重组酶识别位点，其中小鼠进一步包含识别位点特异性重组酶识别位点的位点特异性重组酶，其中在暴露时诱导重组酶对他莫昔芬的小鼠。暴露于他莫昔芬后，重组酶被表达并作用于RRS侧翼的突变外显子5上，并将突变外显子5置于有义方向，并删除了野生型外显子。

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公开/公告号US10470444B2

专利类型
公开/公告日2019-11-12

原文格式PDF
申请/专利权人 REGENERON PHARMACEUTICALS INC.;
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申请/专利号US201816175758
发明设计人 ARIS N. ECONOMIDES;SARAH JANE HATSELL;
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申请日2018-10-30
分类号C12N15;A01K67/027;C07K14/71;C12N15/85;
国家 US
入库时间 2022-08-21 11:30:30

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Vascular304Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipidsTranscriptional control and RNA species - Vascular307MicroRNA-34a role in vascular calcification308Local delivery of a miR-146a inhibitor utilizing a clinically applicable approach attenuates neointima formation after vascular injury309Long noncoding RNA landscape of hypoxic endothelial cells310Specific circulating microRNAs levels associate with hypertension, hyperglycemia and dysfunctional HDL in acute coronary syndrome patientsCytokines and cellular inflammation - Vascular313Phosphodiesterase5A up-regulation in vascular endothelium under pro-inflammatory conditions: a newly disclosed anti-inflammatory activity for the omega-3polyunsaturated aatty acid docosahexaenoic acid314Cardiovascular risk modifying with extra-low dose anticytokine drugs in rhematoid arthritis315Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation316Lymphocytic myocarditis coincides with increased plaque inflammation and plaque hemorrhage in coronary arteries, facilitating myocardial infarction317Serum osteoprotegerin level predictsdeclined numerous of circulating endothelial- derived and mononuclear-derived progenitor cells in patients with metabolic syndromeGrowth factors and neurohormones - 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