Background: The mouse corneal epithelium is a continuously renewing 5-6 cell thick protective layer covering the corneal surface, which regenerates rapidly when injured. It is maintained by peripherally located limbal stem cells (LSCs) that produce transient amplifying cells (TACs) which proliferate, migrate centripetally, differentiate and are eventually shed from the epithelial surface. LSC activity is required both for normal tissue maintenance and wound healing. Mosaic analysis can provide insights into LSC function, cell movement and cell mixing during tissue maintenance and repair. The present study investigates cell streaming during corneal maintenance and repair and changes in LSC function with age.

We have developed a transgenic animal model to investigate the effects of overexpression of rat prorenin on the cardiovascular system. Two transgenic rat lines were generated in which rat prorenin expression was directed to the liver by a human ␣ 1-antitrypsin promoter. Liver-specific expression was confirmed by RNase protection assay. Plasma prorenin concentrations in transgenic rats were increased 400-fold in the males of both lines but were increased only two-to threefold in the females. Thus, transgene expression exhibited sexual dimorphism. Blood pressures were not significantly higher in transgenic rats than in nontransgenic controls. The ratio of heart weight to body weight was greater in male transgenic rats than in the nontransgenic controls.

The secretion of renin from granules stored in renal juxtaglomerular cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated the Ren-1 d gene, one of two mouse genes encoding renin, and report that lack of renin-1 d results in altered morphology of the macula densa of the kidney distal tubule and complete absence of juxtaglomerular cell granulation. Furthermore, Ren-1 d؊/؊ mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1 d -null mice should provide a tool for the investigation of the JG cell-macula densa signaling. Furthermore, the current data indicate that expression of the Ren-1 d gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1 d and renin-2 are secreted by distinct pathways in vivo.Renin (EC 3.4.23.15) is an aspartyl protease, which catalyzes the first step in the renin angiotensin system, the end product of which is the potent vasopressor peptide hormone, angiotensin II (AngII).1 This octapeptide acts to increase peripheral vascular resistance and promote salt and fluid retention in concert with the hormone aldosterone. Renin is synthesized principally in the kidney juxtaglomerular (JG) cells, a group of modified smooth muscle cells located at the distal end of the renal afferent arteriole of the glomerulus (1). JG cells are in close contact with the macula densa, a specialized plaque of epithelial cells of the kidney distal tubule, which signal to the renal arterioles to regulate glomerular filtration rate and the secretion of renin, in response to ionic concentration and flow rate in the distal tubule (2, 3), the so-called tubuloglomerular feedback loop. Except for the submandibular gland (SMG) of the mouse, the JG cells are the only site where prorenin, the inactive zymogen, is known to be converted to the active form of renin. SMG renin does not, however, make its way into the plasma in large quantities and is thought not to play a significant role in blood pressure regulation under normal circumstances (reviewed in Bing et al. (4)). The release of renin from JG cells is mediated by two pathways: regulated release of the mature, active renin from modified lysosomal storage granules and constitutive release of the inactive zymogen. While the regulated pathway of renin secretion is responsive to baroreceptor, neurogenic, and macula densa signals (5), the physiological significance of the constitutive secretion of prorenin is not understood, nor are the molecular pathways that link secretory signals to renin maturation and release. Clarification of the mechanisms underlying these processes will be crucial to our understanding of the control of ...