Shimada Takashi, Urakawa Itaru, Yamazaki Yuji, Hasegawa Hisashi, Hino Rieko, Yoneya Takashi, Takeuchi Yasuhiro, Fujita Toshiro, Fukumoto Seiji, Yamashita Takeyoshi
Pharmaceutical Research Laboratories, KIRIN Brewery Co. Ltd., 3 Miyahara, Takasaki, 370-1295 Gunma, Japan.
Biochem Biophys Res Commun. 2004 Feb 6;314(2):409-14. doi: 10.1016/j.bbrc.2003.12.102.
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.
成纤维细胞生长因子（FGF）-23被确定为肿瘤诱导性骨软化症的致病因素，也是常染色体显性低磷性佝偻病的致病基因。为阐明FGF-23在这些疾病中的病理生理作用，我们培育了其转基因小鼠。表达人FGF-23的转基因小鼠再现了这些疾病的常见临床特征，如低磷血症（可能是由于肾磷酸盐排泄增加所致）、血清1,25-二羟维生素D水平异常降低以及佝偻病样骨骼。转基因小鼠的肾磷酸盐排泄伴随着肾近端小管中IIa型钠磷共转运蛋白表达的降低。这些结果强化了这样一种观点，即FGF-23的过度作用在几种低磷性佝偻病/骨软化症的发生中起致病作用。
