Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice.
A line of transgenic mice expressing insulin-like growth factor-I (IGF-I) under the control of the mouse metallothionien-1 promoter was crossed to a line of dwarf transgenic mice lacking GH expressing cells that were genetically ablated by diphtheria toxin expression. Mice generated from this cross that carry both transgenes express IGF-I in the absence of GH. These mice grew larger than their GH-deficient transgenic littermates and exhibited weight and linear growth indistinguishable from that of their nontransgenic siblings. These results confirm the suspected role of IGF-I in mediating GH's stimulation of somatic growth, including that of long bones, and illustrates the essential role of GH and IGF-I in the modulation of postnatal growth. Analysis of differences in organ growth among these mice, however, suggests that GH and IGF-I also have growth promoting actions that are independent of one another; GH appears to be necessary for the attainment of normal liver size, while IGF-I can stimulate brain growth.
Behringer
R R
RR
Department of Pediatrics, University of North Carolina, Chapel Hill 27599.
Lewin
T M
TM
Quaife
C J
CJ
Palmiter
R D
RD
Brinster
R L
RL
D'Ercole
A J
AJ
D000375:Aging; D000818:Animals; D001835:Body Weight; D001846:Bone Development; D001921:Brain / Q000254:growth & development; D004167:Diphtheria Toxin / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006128:Growth; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000254:growth & development; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013002:Somatomedins / Q000502:physiology*
D004167:Diphtheria Toxin; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008668:Metallothionein