Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism
| Autor: | Maria Luisa S. Sequeira Lopez, Di Xu, Giulianna R. Borges, Martin D. Cassell, R. Ariel Gomez, Curt D. Sigmund, Deborah R. Davis, Justin L. Grobe, Khristofor Agassandian |
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| Rok vydání: | 2010 |
| Předmět: |
Gene isoform
medicine.medical_specialty Physiology Transgene Blood Pressure Mice Transgenic Biology Kidney Renin-Angiotensin System Mice Internal medicine Renin–angiotensin system Renin Genetics medicine Animals Gene knockout Research Articles Mice Knockout Neurons Kidney metabolism Brain Exons Nestin medicine.anatomical_structure Endocrinology Neuron Basal Metabolism Neuroglia |
| Zdroj: | Physiological genomics. 43(6) |
| ISSN: | 1531-2267 |
| Popis: | The renin-angiotensin system (RAS), known for its roles in cardiovascular, metabolic, and developmental regulation, is present in both the circulation and in many individual tissues throughout the body. Substantial evidence supports the existence of a brain RAS, though quantification and localization of brain renin have been hampered by its low expression levels. We and others have previously determined that there are two isoforms of renin expressed in the brain. The classical isoform encoding secreted renin (sREN) and a novel isoform encoding intracellular renin (icREN), the product of an alternative promoter and first exon (exon 1b). The differential role that these two isoforms play in cardiovascular and metabolic regulation remains unclear. Here we examined the physiological consequences of neuron- and glia-specific knockouts of sREN by crossing mice in which the sREN promoter and isoform-specific first exon (exon-1a) is flanked by LoxP sequences (sRENflox mice) with mice expressing Cre-recombinase controlled by either the neuron-specific Nestin promoter or the glia-specific GFAP promoter. Resulting offspring exhibited selective knockout of sREN in either neurons or glia, while preserving expression of icREN. Consistent with a hypothesized role of icREN in the brain RAS, neuron- and glia-specific knockout of sREN had no effect on blood pressure or heart rate; food, water, or sodium intake; renal function; or metabolic rate. These data demonstrate that sREN is dispensable within the brain for normal physiological regulation of cardiovascular, hydromineral, and metabolic regulation, and thereby indirectly support the importance of icREN in brain RAS function. |
| Databáze: | OpenAIRE |
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