Genetic Knockout and Rescue Studies in Mice Unravel Abnormal Phosphorus Threshold in Hypophosphatemic Rickets

• Published in: Endocrinology (Philadelphia) Vol. 158; no. 3; pp. 455 - 457
• Main Authors: Sanchez, Cheryl P., Mohan, Subburaman
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.03.2017; Oxford University Press
• Subjects: Animals; Endocrinology; Familial Hypophosphatemic Rickets - genetics; Gene Knockout Techniques; Hypophosphatemia; Mice; Mice, Knockout; Phosphorus; Rickets; Rickets - genetics; Rickets, Hypophosphatemic - genetics; Views
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2017-00030

Maintaining phosphate homeostasis is of crucial biological importance for overall general health as inorganic phosphorus plays an important role in multiple biological processes, including skeletal mineralization, energy production, cell signaling, and regulation of protein function. Phosphate comprises -1% of total body weight, of which -85% is present in bone and teeth. The serum phosphate level is subject to regulation by dietary phosphate levels in addition to the gastrointestinal-bone-renal axis through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular absorption (1). In the small intestine, phosphate is absorbed by paracellular transport, which depends on passive transfusion, and active transport, which occurs mainly through the sodium-dependent phosphate cotransporter sodium-dependent phosphate cotransporter (NPT)2b (2). In the kidney, most phosphate filtered through glomeruli is reabsorbed in proximal tubules via NPT2a and NPT2c (3).