Endothelial cell expression of mutant Map2k1 causes vascular malformations in mice.

ABSTRACT: Extracranial arteriovenous malformation (AVM) is a congenital vascular anomaly causing disfigurement, bleeding, ulceration, and pain. Most lesions are associated with somatic MAP2K1 activating mutations in endothelial cells (ECs). The purpose of this study was to determine if EC expression of mutant activated MAP2K1 is sufficient to produce vascular malformations in mice. We generated mice with a ROSA26 allele containing a lox-stop-lox gene trap (GT), Map2k1 cDNA with an activating p.K57N missense mutation, an internal ribosomal entry site, and green fluorescent protein cDNA (R26^{GT-Map2k1-GFP}). We expressed mutant MAP2K1 and GFP in ECs of fetal and newborn mice using Tg-Cdh5Cre or Tg-Cdh5CreER alleles. Tg-Cdh5Cre^+/-;R26^{GT-Map2k1-GFP/+} animals that express m

SUBMITTER: Smits PJ 

PROVIDER: S-EPMC9918623 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature