FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.
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.
Shimada
Takashi
T
Pharmaceutical Research Laboratories, KIRIN Brewery Co. Ltd., 3 Miyahara, Takasaki, 370-1295 Gunma, Japan.
Urakawa
Itaru
I
Yamazaki
Yuji
Y
Hasegawa
Hisashi
H
Hino
Rieko
R
Yoneya
Takashi
T
Takeuchi
Yasuhiro
Y
Fujita
Toshiro
T
Fukumoto
Seiji
S
Yamashita
Takeyoshi
T
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
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