Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Cre/loxP and Flp/FRT systems mediate site-specific DNA recombination and are being increasingly utilized to study gene function in vivo. These systems allow targeted gene disruption in a single cell type in vivo, thereby permitting study of the physiological and pathophysiological impact of a given gene product derived from a particular cell type. In the kidney, the Cre/loxP system has been employed to achieve gene deletion selectively within principal cells of the collecting duct. Disruption of target genes in the collecting duct, such as endothelin-1 or polycystic kidney disease-1 (PKD1), could lead to important insights into the biological roles of these gene products. With selection of the appropriate renal cell-specific promoters, these recombination systems could be used to target gene disruption to virtually any renal cell type. Although transgenic studies utilizing these recombination systems are promising, they are in their relative infancy and can be time consuming and expensive and yield unanticipated results. It is anticipated that continued experience with these systems will produce an important tool for analyzing gene function in renal health and disease.
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PMID:The Cre/loxP system and gene targeting in the kidney. 1033 46

Conditional gene targeting technique, which is based on the use of Cre-loxP or Flp/FRT systems, has been increasingly used to study gene function of a particular cell type in vivo. The introduction of this technique to the kidney field is relatively recent but has already provided important insights into physiological or pathological functions of a number of genes in the kidney. This technique has recently been used to inactivate the peroxisome proliferator-activated receptor subtype gamma in the collecting duct, which leads to remarkable blockade of body weight gains and plasma volume expansion associated with thiazolidinediones. This finding not only helps understand pharmacology of the novel class of antidiabetic drugs, but also uncovers an important role of peroxisome proliferator-activated receptor subtype gamma in regulation of distal nephron fluid reabsorption. The present review represents an example for the use of the modern technique to address complex clinical problems. It is anticipated that over next few years this technique will be used by an increasing number of investigators for studying gene function in the kidney.
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PMID:Kidney-specific gene targeting: insight into thiazolidinedione-induced fluid retention. 1675 32

Sgk1 is an aldosterone-induced kinase that regulates epithelial sodium channel (ENaC)-mediated Na+ transport in the collecting duct and connecting tubule of the kidney. The NH2 terminus of Sgk1 contains instability motifs that direct the ubiquitination of Sgk1 resulting in a rapidly degraded protein. By bioinformatic analysis, we identified a 5' variant alternate transcript of human Sgk1 (Sgk1_v2) that is widely expressed, is conserved from rodent to humans, and is predicted to encode an Sgk1 isoform, Sgk1_i2, with a different NH2 terminus. When expressed in HEK293 cells, Sgk1_i2 was more abundant than Sgk1 because of an increased protein half-life and this correlated with reduced ubiquitination of Sgk1_i2 and enhanced surface expression of ENaC. Immunocytochemical studies demonstrated that in contrast to Sgk1, Sgk1_i2 is preferentially targeted to the plasma membrane. When coexpressed with ENaC subunits in FRT epithelia, Sgk1_i2 had a significantly greater effect on amiloride-sensitive Na+ transport compared with Sgk1. Together, the data demonstrate that a conserved NH2-terminal variant of Sgk1 shows improved stability, enhanced membrane association, and greater stimulation of epithelial Na+ transport in a heterologous expression system.
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PMID:An evolutionarily conserved N-terminal Sgk1 variant with enhanced stability and improved function. 1875 99