title: FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.
abstract: Fibroblast growth factor (FGF)-23 was identified as a causative factor of tumor-induced osteomalacia and also as a responsible gene for autosomal dominant hypophosphatemic rickets. To clarify the pathophysiological roles of FGF-23 in these diseases, we generated its transgenic mice. The transgenic mice expressing human FGF-23 reproduced the common clinical features of these diseases such as hypophosphatemia probably due to increased renal phosphate wasting, inappropriately low serum 1,25-dihydroxyvitamin D level, and rachitic bone. The renal phosphate wasting in the transgenic mice was accompanied by the reduced expression of sodium phosphate cotransporter type IIa in renal proximal tubules. These results reinforce the notion that the excessive action of FGF-23 plays a causative role in the development of several hypophosphatemic rickets/osteomalacia.
authors.affiliation: Pharmaceutical Research Laboratories, KIRIN Brewery Co. Ltd., 3 Miyahara, Takasaki, 370-1295 Gunma, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Itaru
authors.initials: I
authors.lastname: Urakawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Rieko
authors.initials: R
authors.lastname: Hino
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoneya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000000981:diagnostic imaging; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids / Q000378:metabolism; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012279:Rickets / Q000235:genetics*; D050608:Sodium-Phosphate Cotransporter Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution; D019076:Transgenes; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; C493554:SLC34A1 protein, human; C493555:Slc34a1 protein, mouse; D050608:Sodium-Phosphate Cotransporter Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23