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纤溶酶原激活物抑制剂-1基因缺陷小鼠。I. 通过同源重组产生及特性分析。

Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by homologous recombination and characterization.

作者信息

Carmeliet P, Kieckens L, Schoonjans L, Ream B, van Nuffelen A, Prendergast G, Cole M, Bronson R, Collen D, Mulligan R C

机构信息

Whitehead Institute for Biomedical Sciences, Cambridge, Massachusetts 02139-4307.

出版信息

J Clin Invest. 1993 Dec;92(6):2746-55. doi: 10.1172/JCI116892.

DOI:10.1172/JCI116892
PMID:8254028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC288473/
Abstract

Homozygous plasminogen activator inhibitor-1 (PAI-1)-deficient (PAI-1-/-) mice were generated by homologous recombination in D3 embryonic stem cells. Deletion of the genomic sequences encompassing the transcription initiation site and the entire coding regions of murine PAI-1 was demonstrated by Southern blot analysis. A 3.0-kb PAI-1-specific mRNA was identified by Northern blot analysis in liver from PAI-1 wild type (PAI-1+/+) but not from PAI-1-/- mice. Plasma PAI-1 levels, measured 2-4 h after endotoxin (2.0 mg/kg) injection were 63 +/- 2 ng/ml, 30 +/- 10 ng/ml, and undetectable (< 2 ng/ml) in PAI-1+/+, heterozygous (PAI-1+/-) and PAI-1-/- mice, respectively (mean +/- SEM, n = 4-11). PAI-1-specific immunoreactivity was demonstrable in kidneys of PAI-1+/+ but not of PAI-1-/- mice. SDS-gel electrophoresis of plasma incubated with 125I-labeled recombinant human tissue-type plasminogen activator revealed an approximately 115,000-M(r) component with plasma from endotoxin-stimulated (0.5 mg/kg) PAI-1+/+ but not from PAI-1-/- mice, which could be precipitated with a polyclonal anti-PAI-1 antiserum. PAI-1-/- mice were viable, produced similar sizes of litters as PAI-1+/+ mice, and showed no apparent macroscopic or microscopic histological abnormalities.

摘要

通过在D3胚胎干细胞中进行同源重组，培育出了纯合型纤溶酶原激活物抑制剂-1（PAI-1）缺陷（PAI-1-/-）小鼠。通过Southern印迹分析证实了包含小鼠PAI-1转录起始位点和整个编码区的基因组序列缺失。通过Northern印迹分析在PAI-1野生型（PAI-1+/+）小鼠肝脏中鉴定出3.0 kb的PAI-1特异性mRNA，而在PAI-1-/-小鼠肝脏中未鉴定到。在内毒素（2.0 mg/kg）注射后2 - 4小时测量的血浆PAI-1水平，在PAI-1+/+、杂合子（PAI-1+/-）和PAI-1-/-小鼠中分别为63±2 ng/ml、30±10 ng/ml和未检测到（<2 ng/ml）（平均值±标准误，n = 4 - 11）。PAI-1特异性免疫反应性在PAI-1+/+小鼠肾脏中可检测到，而在PAI-1-/-小鼠肾脏中未检测到。用125I标记的重组人组织型纤溶酶原激活物孵育血浆后的SDS凝胶电泳显示，在内毒素刺激（0.5 mg/kg）的PAI-1+/+小鼠血浆中有一个约115,000-M(r)的成分，而在PAI-1-/-小鼠血浆中没有，该成分可用多克隆抗PAI-1抗血清沉淀。PAI-1-/-小鼠存活，产仔大小与PAI-1+/+小鼠相似，且未表现出明显的宏观或微观组织学异常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/e8c8706457b6/jcinvest00044-0202-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/e249ff2c39a6/jcinvest00044-0198-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/7133a0619ff4/jcinvest00044-0198-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/ca1a8b86aaa0/jcinvest00044-0198-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/6865d1b5fd32/jcinvest00044-0198-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/d42996e702e9/jcinvest00044-0199-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/6bddf74caf96/jcinvest00044-0199-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/2dfb2af03f27/jcinvest00044-0200-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/9d1d08c1ffe7/jcinvest00044-0202-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/e8c8706457b6/jcinvest00044-0202-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/e249ff2c39a6/jcinvest00044-0198-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/7133a0619ff4/jcinvest00044-0198-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/ca1a8b86aaa0/jcinvest00044-0198-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/6865d1b5fd32/jcinvest00044-0198-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/d42996e702e9/jcinvest00044-0199-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/6bddf74caf96/jcinvest00044-0199-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/2dfb2af03f27/jcinvest00044-0200-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/9d1d08c1ffe7/jcinvest00044-0202-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c735/288473/e8c8706457b6/jcinvest00044-0202-b.jpg

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