Insulin-like growth factor I regulates renal development in rodents

Blocking the action of insulin-like growth Factor I (IGF I) impairs kidney development in vitro. However, no renal developmental abnormalities have be en reported in newborn transgenic mice that do not express IGF I (Igf1(-/-) ) mice. Ninety-five percent of Igf1(-/-) mice die immediately following bir th. Kidney development continues Following birth in rodents. To readdress t he question of the participation of IGF I in the process of kidney developm ent, we measured nephron numbers in developed kidneys from lgf1(-/-) mice t hat survived past birth, and using a second model of kidney development, ch aracterized the effect of IGF infused into rat hosts on the renal function of transplanted metanephroi. lgf1(-/-) mice were born with grossly normal k idneys. At 77 +/- 10 days after birth, lgf1(-/-)mice that survived were app roximately 28% the weight of wild-type (WT) littermates and had proportiona lly smaller kidneys, The number of nephrons per kidney was reduced by appro ximately 20% in lgf1(-/-) mice. Glomerular size was also reduced in lgf1(-/ -) mice. In untreated host rats, neither the size nor insulin clearance of transplanted metanephroi changed significantly from 12-28 weeks postimplant ation. The administration of IGF I to hosts did not affect the size of tran splanted metanephroi measured at 12-16 weeks following implantation. Howeve r, inulin clearances were increased significantly by the administration of IGF I to hosts. Our findings 1) indicate that IGF I plays a role in determi ning nephron number, 2) suggest that it enhances function in developing kid neys, and 3) establish the potential for the pharmacological use of IGF I t o enhance the growth and function of transplanted metanephroi. (C) 1999 Wil ey-Liss, Inc.