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Physiol. Genomics 16: 240-246, 2004. First published November 18, 2003; doi:10.1152/physiolgenomics.00131.2003
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Localization of renin expressing cells in the brain, by use of a REN-eGFP transgenic model

¹ Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242
² Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242
³ Roswell Park Cancer Institute, Buffalo, New York 14263

Immunoreactive renin has been reported in the hypothalamus and cerebellar cortex in the rodent brain and in neurons in all areas of the human brain. Despite these observations and the clear documentation of the expression of the other renin-angiotensin system genes in the brain, the notion that renin is endogenously expressed in the brain remains very controversial and undefined. This controversy no doubt arises because the level of renin expression in the brain is below the detection threshold of most standard assays. A transgenic mouse expressing enhanced green fluorescence protein (eGFP) under the control of the mouse renin promoter was recently reported. This model expresses eGFP in the kidney, which responds appropriately to both developmental and physiological stimuli. We therefore used eGFP as a sensitive marker to identify renin-expressing cells in the brain. We identified eGFP-containing cells in specific areas of the brain, including cerebellum, hippocampus, dorsal motor nucleus of the vagus, inferior olivary nucleus, reticular formation, rostral ventrolateral medulla, central nucleus of the amygdala, lateral parabrachial nucleus, mesencephalic trigeminal nucleus, bed nucleus of stria terminalis, and subfornical organ. By colabeling with neuron- or glia (astrocytes or oligodendrocytes)-specific antisera, we have determined the eGFP-positive cells to be mainly neuronal. These findings therefore strongly support the primary expression of renin mRNA in the brain in regions controlling cardiovascular function.

ACE/angiotensin receptors, gene expression, genetically altered mice; renin; brain; neuron; astrocyte; oligodendrocytes

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