Endothelial cell-specific knockout of connexin 43 causes hypotension and bradycardia in mice
| Autor: | Brian R. Duling, D. N. Damon, Kathy H. Day, Yongbo Liao |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cell signaling
Endothelium Transgene Recombinant Fusion Proteins Cre recombinase Connexin Cell Communication Biology Regulatory Sequences Nucleic Acid Nitric Oxide Mice Viral Proteins medicine Bradycardia Genes Synthetic Animals Homeostasis Transgenes Promoter Regions Genetic Regulation of gene expression Mice Knockout Recombination Genetic Multidisciplinary Integrases Angiotensin II Gap Junctions Receptor Protein-Tyrosine Kinases Exons Biological Sciences Molecular biology Receptor TIE-2 Cell biology Endothelial stem cell Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Organ Specificity Connexin 43 Models Animal cardiovascular system Vascular Resistance sense organs Endothelium Vascular biological phenomena cell phenomena and immunity Angiotensin I Hypotension Gene Deletion |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 98(17) |
| ISSN: | 0027-8424 |
| Popis: | Connexin 43 (Cx43) is a protein expressed in a variety of mammalian tissues. However, the lack of specific blockers and the absence of known genetic mutants have hampered the investigation of the function of this protein. Cx43-null mice die shortly after birth, thus preventing functional studies in vivo . Here, we report the generation and characterization of a vascular endothelial cell-specific deletion of the Cx43 gene (VEC Cx43 KO) in mice by using the loxP/Cre system. Using homologous recombination, a mouse line was created carrying loxP sites flanking exon 2 of the Cx43 gene (“floxed” mice). To produce cell specific deletion of the Cx43 gene, these mice were crossed with animals from a line carrying the Tie 2-Cre transgene. The homozygous VEC Cx43 KO mice survived to maturity. However, they were hypotensive and bradycardic when compared with heterozygous VEC Cx43 KO mice, or to the floxed Cx43 gene mice. The hypotension was associated with marked elevation of plasma nitric oxide (NO) levels as well as elevated plasma angiotensin (Ang) I and II. We hypothesize that endothelial cell Cx43 plays a key role in the formation and/or action of NO, and that the elevation of Ang II is a secondary event. The specific cellular basis for the hypotension remains to be established, but our findings support the idea that endothelial Cx43 gap junctions are involved in maintaining normal vascular function; moreover, these animals provide the opportunity to determine more clearly the role of endothelial Cx43 in vascular development and homeostasis. |
| Databáze: | OpenAIRE |
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