The Murine Stanniocalcin 1 Gene Is Not Essential for Growth and Development

Abstract

The stanniocalcin 1 (STC1) gene is expressed in a wide variety of tissues, including the kidney, prostate, thyroid, bone, and ovary. STC1 protein is considered to have roles in many physiological processes, including bone development, reproduction, wound healing, angiogenesis, and modulation of inflammatory response. In fish, STC1 is a hormone that is secreted by the corpuscles of Stannius and is involved in calcium and phosphate homeostasis. To determine the role of STC1 in mammals, we generated Stc1-null mice by gene targeting. The number of Stc1 ؊/؊ mice obtained was in accordance with Mendelian ratios, and both males and females produced offspring normally. No anatomical or histological abnormalities were detected in any tissues. Our results demonstrated that Stc1 function is not essential for growth or reproduction in the mouse.Stanniocalcin 1 (STC1) is a glycoprotein that was first identified in fish as a hormone secreted by the corpuscles of Stannius, an organ unique to bony fish. It is secreted into the blood in response to elevated calcium and has potent activity on the gills, kidneys, and gut to regulate calcium absorption and phosphate excretion (8,16,17). We and others have identified two related mammalian genes encoding STC1 and STC2 that are paralogs of the fish gene (2,4,6,11,20,21). Mammalian STCs are expressed in a wide variety of tissues, including the kidney, ovary, prostate, thyroid, and spleen.Given its role in fish, initial functional analyses of mammalian STC1 focused on determining whether its role in regulating blood calcium has been conserved. In vivo studies in which recombinant STC1 protein was injected into rats indicated that STC1 may regulate blood calcium by increasing renal reabsorption of phosphate, and in vitro experiments showed that STC1 could reduce the flux of calcium across the intestines of rats and swine while increasing absorption of phosphate (19,21,27). Interestingly, expression studies showed strong STC1 production in a variety of tissues during murine development and a general down-regulation of expression during postnatal development in all tissues except the ovary, where expression increased. On the basis of these and a variety of other functional and expression studies, it has been proposed that the physiologic roles of STC1 are pleiotropic and include early musculoskeletal development, female reproduction, cell motility, and a cytoprotective role in response to different stressors (13-15, 22, 24, 31-34). Moreover, evidence is also accumulating for a role of STC1 in cancer (reviewed in reference 3).To determine whether STC1 plays a crucial role during normal development and provide a model for examining the function of STC1 in vivo, we generated mice that are null for STC1. We generated two independent lines (L278 and L282) by homologous recombination and examined them for overt abnormalities. MATERIALS AND METHODSTargeting vector construction and generation of Stc1-deficient mice. Genomic DNA encoding STC1 was isolated from a mouse 129 SVJ Lambda FIXII library (...

Expression and regulation of stanniocalcin 1 and 2 in rat uterus during embryo implantation and decidualization

“…The authors could not find any important change in fertility in STC-1 null mice, the histological examination of the uterus and ovary did not show any abnormalities compared with wild-type mice (Chang et al 2005). The authors also ruled out the possibility of STC-2 compensating for the loss of STC-1, but checked STC-2 expression under normal status only.…”

Glial-derived neurotrophic factor promotes ovarian primordial follicle development and cell–cell interactions during folliculogenesis

“…Further studies described an increase in STC1 expression during pregnancy and lactation, and a possible function in luteinization inhibition (Ishibashi & Imai 2002, Luo et al 2004. STC1 knockout mice develop as phenotypically and reproductively normal (Chang et al 2005). CTGF is a matrix-associated protein with many possible roles in development and differentiation processes (Leask & Abraham 2003).…”

Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress

“…Establishing the functional importance and relevance of these putative functions has proved difficult; moreover, STC1-null mice housed in standard laboratory conditions have no obvious phenotype (Chang et al, 2005).…”