Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 11;28(3):33.
doi: 10.1007/s10456-025-09986-4.

An endothelial specific mouse model for the capillary malformation mutation Gnaq p.R183Q

Patrick Smits  1 , Leanna Marrs  2 , Yu Sheng Cheng  2 , Michal Ad  2 , Sana Nasim  3 , David Zurakowski  4 , Joyce Bischoff  3 , Arin K Greene  2
Affiliations

An endothelial specific mouse model for the capillary malformation mutation Gnaq p.R183Q

Patrick Smits et al. Angiogenesis. .

Abstract

Capillary malformation (CM) is a congenital, non-hereditary lesion composed of enlarged and tortuous blood vessels. CM is associated with a somatic p.R183Q activating mutation in the Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene in endothelial cells (EC). Cutaneous CMs are present in 1/300 infants and in 55-70% of CM cases soft tissue overgrowth is observed. Pharmacotherapy for CM does not exist. Here we report a conditional mouse model allowing the simultaneous tissue specific expression of GNAQ p.R183Q and Green Fluorescent Protein (GFP) from the Rosa26 (R26) locus (R26GT - Gnaq-GFP). We show that expression of GNAQ p.R183Q in ECs results in vascular malformations with features similar to human CM lesions. GNAQ p.R183Q expression during embryonic development (Tg-Cadherin5Cre (Tg-Cdh5Cre)) resulted in a severe vascular phenotype, lethal by embryonic (E) 16.5. Sporadic induction of mutant GNAQ expression in ECs at postnatal (P) day 1 (Tg-Cdh5CreER) led to tortuous and enlarged blood vessels, most noticeable in the intestines. GNAQ p.R183Q/GFP expressing ECs co-localized with lesions and displayed increased proliferation. Mutant ECs had abnormal mural cell coverage and abnormal pericellular extracellular matrix deposition, which was confirmed in human CM samples. Similar to human CM they displayed strong expression of the tip cell marker Endothelial cell-specific molecule 1 (ESM1) and increased Angiopoietin 2 (ANGPT2) expression. In conclusion, GNAQ p.R183Q expression in mouse ECs causes vascular malformations supporting the mutation's causality for CM. The lesions recapitulate multiple features of human CM, making the mouse model suitable for the preclinical testing of future CM pharmacotherapy.

Keywords: Capillary malformation; Cdh5Cre; Cdh5CreER; Conditional R26 allele; Disease model; Endothelial; GNAQ pR183Q; Mouse.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Research reported in this publication was supported by: NIH (NHLBI)-2R01HL127030 (AKG, JB), NIH (NICHD)-T32 HD104582-01A1 (MA), F32HL172637 and K99HL177326 (SN), the Taylor/McDonald Family, and P50 HD105351 (IDDRC Gene Manipulation & Genome Editing Core Boston Children’s Hospital). The content of this research is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Update of

References

    1. Jacobs AH, Walton RG (1976) The incidence of birthmarks in the neonate. Pediatrics 58:218–222 - DOI - PubMed
    1. Gupta A, Kozakewich H (2011) Histopathology of vascular anomalies. Clin Plast Surg 38:31–44 - DOI - PubMed
    1. Tan W, Wang J, Zhou F, Gao L, Yin R, Liu H, Sukanthanag A, Wang G, Mihm MC Jr., Chen DB et al (2017) Coexistence of Eph receptor B1 and Ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation. Br J Dermatol 177:1601–1611 - DOI - PubMed - PMC
    1. Greene AK, Taber SF, Ball KL, Padwa BL, Mulliken JB (2009) Sturge-Weber syndrome: soft-tissue and skeletal overgrowth. J Craniofac Surg 20(Suppl 1):617–621 - DOI - PubMed
    1. Desai S, Glasier C (2017) Sturge-Weber syndrome. N Engl J Med 377:e11 - DOI - PubMed

Substances

LinkOut - more resources