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
© 2023 The Authors. genesis published by Wiley Periodicals LLC..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Genesis (New York, N.Y. : 2000) - 62(2024), 1 vom: 01. Feb., Seite e23539 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lartey, Nathaniel L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.04.2024 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/dvg.23539 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360012752 |
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| 100 | 1 | |a Lartey, Nathaniel L |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a 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 |
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| 520 | |a © 2023 The Authors. genesis published by Wiley Periodicals LLC. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Letter | |
| 650 | 4 | |a Ras signal transduction | |
| 650 | 4 | |a basement membrane | |
| 650 | 4 | |a blood vessels | |
| 650 | 4 | |a capillary malformation–arteriovenous malformation | |
| 650 | 4 | |a developmental angiogenesis | |
| 650 | 4 | |a endothelial cell | |
| 650 | 4 | |a type IV collagen | |
| 650 | 4 | |a vascular disease | |
| 650 | 7 | |a Collagen Type IV |2 NLM | |
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| 700 | 1 | |a Alonzo, Roxann |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Di |e verfasserin |4 aut | |
| 700 | 1 | |a King, Philip D |e verfasserin |4 aut | |
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