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

Renal failure was diagnosed in 22 young Doberman Pinscher dogs. The clinical findings were anorexia, weight loss, vomiting, lethargy, polydipsia, polyuria, and dehydration. Laboratory findings were azotemia, hyperphosphatemia, lymphopenia, nonregenerative anemia, hypercholesterolemia, and proteinuria. The kidneys were characterized pathologically by glomerular sclerosis, cystic glomerular atrophy, tubular dilatation, tubular atrophy, mononuclear interstitial inflammation, interstitial fibrosis, interstitial mineralization, and hyperplasia of the collecting duct epithelium.
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PMID:Juvenile renal disease in Doberman Pinscher dogs. 683 84

Inactivation of the transcription factor AP-2 beta in a genetically mixed C57BL/6/129S1 mouse strain resulted in perinatal lethality as a consequence of massively enhanced apoptotic death of renal epithelial cells (Genes Dev 1997;11:1938-1948). Recently, we observed that the phenotype is modulated by genetic background because AP-2 beta mutant mice, backcrossed onto 129P2 background, survive approximately 2 weeks after birth, allowing for a detailed analysis of kidney function. Here we show that kidneys reveal varying amounts of cysts derived from all tubular structures (proximal and distal tubuli, collecting ducts). However, all mice died irrespective of the degree of cyst formation. Serum analysis of AP-2 beta mutant animals revealed defective tubular secretory function and ion homeostasis including severe hypocalcemia, hyperphosphatemia, and hyperuremia. Because hormonal calcium regulation was not impaired, the mice developed secondary renal hyperparathyroidism as typically observed in patients with terminal renal failure. We further demonstrate that molecular defects in the collecting duct system lead to insufficient water retention and urinary concentration. In summary, our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions.
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PMID:Terminal renal failure in mice lacking transcription factor AP-2 beta. 1269 60

The Na+/H+ exchanger isoform 3 (NHE3) facilitates Na+ absorption and H+ secretion and is expressed in the intestine, proximal tubule, and thick ascending limb of the kidney. While the function of NHE3 for Na+ and [Formula: see text](re)absorption has been defined using conventional NHE3 knockout mice (NHE3-/-), the recent generation of conditional NHE3 knockout mice started to give critical new insight into the role of this protein by allowing for temporal and spatial control of NHE3 expression. For example, in contrast to NHE3-/- mice, knockout of NHE3 in the S1 and S2 segments of the proximal tubule or along the entire tubule/collecting duct does not cause any lethality. Nonabsorbable NHE3 inhibitors have been developed, and preclinical as well as clinical trials indicate possible pharmacological use in fluid overload, hypertension, chronic kidney disease, hyperphosphatemia, and constipation. Some of the therapeutic considerations seem to be directly related to the pharmacodynamic properties of these drugs; however, little is known about the effects of these nonabsorbable NHE3 inhibitors on intestinal phosphate transport and the mechanisms so far remain elusive. This review focuses on novel findings of NHE3 in the intestine and the kidney as well as novel drug developments targeting NHE3.
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PMID:Novel developments in differentiating the role of renal and intestinal sodium hydrogen exchanger 3. 2825 10