Work

Hyperactive GNAQ in endothelial cells causes blood vessel malformation in developing mouse skin

Year: 2026

Type: article

Abstract: Vascular anomalies are a group of congenital disorders characterized by structural abnormalities in the blood vessels. Over the past 20 years, genetic investigations have identified mosaic mutations in multiple genes in individuals with vascular anomalies, including G protein alpha subunit q/11-encoding genes GNAQ/GNA11. Here, we report a tunable and reversible mouse tool for studying the frequent GNAQ mutant, GNAQ R183Q. We have generated a transgenic mouse line carrying GNAQ R183Q under the control of the tet-responsive elements. The transgene expression level is tunable and can be induced at physiologically relevant ranges. We have shown that endothelial expression of GNAQ R183Q is sufficient to drive blood vessel malformation in developing mouse embryos. We have further identified multiple transcriptional changes caused by GNAQ R183Q in the skin using RNA-seq. This work strengthens the causal link between GNA mutations and vascular anomalies, demonstrates that endothelial cell-specific expression of GNAQ R183Q is sufficient to cause vascular defects during development, and offers valuable insights into the mechanisms underlying GNA mutation-associated diseases.

Source: Development

DOI: 10.1242/dev.204936

Authors: Jenna Meyers, Zach Tower, Olivia Leighton, Beth Drolet, Hao Chang

Institutions: University of Wisconsin–Madison, William S. Middleton Memorial Veterans Hospital

Language: English

Topic: Vascular Malformations and Hemangiomas

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: University of Wisconsin-Madison, Pediatric Dermatology Research Alliance, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases