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. 2021 Apr 1;35(7-8):495–511. doi: 10.1101/gad.348221.120

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© 2021 Driskill et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Figure 1. — TAZ-CAMTA1 expression in endothelial cells drives the formation of EHE-like vascular tumors in the lungs of mice. (A) Structure of TAZ, CAMTA1, and the resulting TAZ-CAMTA1 fusion protein formed from the t(1;3)(p36;q25) chromosomal translocation. TAZ-CAMTA1 contains the N terminus of TAZ with its TEAD-binding domain (TBD), WW domain, and three LATS1/2 phosphorylation sites, and the C terminus of CAMTA1 with its transcription activation domain (TAD), TIG domain, ankyrin repeats (ANK), IQ motifs, and a nuclear localization signal (NLS). TAZ-CAMTA1 has lost the TAD of TAZ, one of TAZ's LATS1/2 phosphorylation sites, and the CG-1 domain of CAMTA1. (B) Schematics of the Cdh5-tTA and TRE-TAZ-CAMTA1 alleles for endothelial-specific expression of TAZ-CAMTA1. (C) Schematic for induction of TAZ-CAMTA1 expression after birth. (D) Survival curve for Ctrl (single transgenic Cdh5-tTA or TRE-TAZ-CAMTA1 mice, n = 14, median survival = undefined) or TAZ-CAMTA1^iEC mice (Cdh5-tTA;TRE-TAZ-CAMTA1, n = 20, median survival = 39.5 d). (****) P < 0.0001, Mantel-Cox test. (E–I) Representative images showing H&E (E,F), CD31 (G), CD34 (H), and Erg (I) immunohistochemistry of a tumor found within a vessel of the lungs of 7-wk-old TAZ-CAMTA1^iEC mice. Black arrows in E point to the tumor, and blue arrows in F show plump spindled and epithelioid cells, while green arrows show cytoplasmic vacuoles, some with red blood cells. Red arrows in G– I show positive staining for the respective markers. Scale bars: E, 100 µm; F––I, 35 µm.