| First Author | Lartey NL | Year | 2024 |
| Journal | Genesis | Volume | 62 |
| Issue | 1 | Pages | e23539 |
| PubMed ID | 37501352 | Mgi Jnum | J:347708 |
| Mgi Id | MGI:7624544 | Doi | 10.1002/dvg.23539 |
| Citation | Lartey NL, et al. (2024) A temporally-restricted pattern of endothelial cell collagen 4 alpha 1 expression during embryonic development determined with a novel knockin Col4a1-P2A-eGFP mouse line. Genesis 62(1):e23539 |
| abstractText | Classical collagen type IV comprising of a heterotrimer of two collagen IV alpha 1 chains and one collagen IV alpha 2 chain is the principal type of collagen synthesized by endothelial cells (EC) and is a major constituent of vascular basement membranes. In mouse and man, mutations in genes that encode collagen IV alpha 1 and alpha 2 result in vascular dysfunction. In addition, mutations in genes that encode the Ephrin receptor B4 (EPHB4) and the p120 Ras GTPase-activating protein (RASA1) that cause increased activation of the Ras mitogen-activated protein kinase (MAPK) signaling pathway in EC result in vascular dysfunction as a consequence of impaired export of collagen IV. To understand the pathogenesis of collagen IV-related vascular diseases and phenotypes it is necessary to identify at which times collagen IV is actively synthesized by EC. For this purpose, we used CRISPR/Cas9 targeting in mice to include immediately after the terminal Col4a1 codon a sequence that specifies a P2A peptide followed by enhanced green fluorescent protein (eGFP). Analysis of eGFP expression in Col4a1-P2A-eGFP mice revealed active embryonic EC synthesis of collagen IV alpha 1 through mid to late gestation followed by a sharp decline before birth. These results provide a contextual framework for understanding the basis for the varied vascular abnormalities resulting from perturbation of EC expression and export of functional collagen IV. |
