Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice

被引:406
作者
Schlaeger, TM
Bartunkova, S
Lawitts, JA
Teichmann, G
Risau, W
Deutsch, U
Sato, TN
机构
[1] BETH ISRAEL HOSP,DEACONESS MED CTR,BOSTON,MA 02215
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02215
[3] MAX PLANCK INST PHYSIOL & CLIN RES,D-61231 BAD NAUHEIM,GERMANY
关键词
transcription; enhancer;
D O I
10.1073/pnas.94.7.3058
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
TIE2 is a vascular endothelial-specific receptor tyrosine kinase essential for the regulation of vascular network formation and remodeling. Previously, we have shown that the 1.2-kb 5' flanking region of the TIE2 promoter is capable of directing beta-galactosidase reporter gene expression specifically into a subset of endothelial cells (ECs) of transgenic mouse embryos, However, transgene activity: was restricted to early embryonic stages and not detectable rn adult mice, Herein we describe the identification and characterization of an autonomous endothelial-specific enhancer in the first intron of the mouse TIE2 gene, Furthermore, combination of the TIE2 promoter with an intron fragment containing this enhancer allows it to target reporter gene expression specifically and uniformly to virtually all vascular ECs throughout Embryogenesis and adulthood, To our knowledge, this is the first time that an in, vivo expression system has been assembled by which heterologous genes can be targeted exclusively to the ECs of the entire vasculature. This should he a valuable tool to address the function of genes during physiological and pathological processes of vascular ECs in vivo. Furthermore, we were able to identify a short region critical for enhancer function in vivo that contains putative binding sites for Ets-like transcription factors, This should, therefore, allow us to determine the molecular mechanisms underlying the vascular-EC-specific expression of the TIE2 gene.
引用
收藏
页码:3058 / 3063
页数:6
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