SKELETAL GROWTH OF TRANSGENIC MICE WITH ELEVATED LEVELS OF CIRCULATING INSULIN-LIKE GROWTH FACTOR-II

Insulin-like growth factor-II (IGF-II) is a major factor produced by s keletal tissues, To evaluate endocrine effects of IGF-II on bone growt h, we measured skeletal dimensions of 12-week-old transgenic mice harb ouring fusion genes where a human IGF-Il cDNA is transcriptionally con trolled by rat phospheonolpyruvate carboxykinase (PEPCK) promoter sequ ences, Transgene expression in liver, kidney and intestine resulted in circulating IGF-II levels in transgenic mice which were 2-3-fold high er than in controls. Serum IGF-I concentrations of transgenic mice wer e lower than in controls, Body weight was not influenced by the expres sion of the IGF-II transgene, Only 1 out of 5 measurements taken from the radius was significantly affected by the presence of the transgene , while in 60 measurements taken from eight other bones there was no d ifference between transgenic mice and controls, Furthermore, serum lev els of calcium and phosphate as well. as alkaline phosphatase activity were not significantly altered in PEPCK-IGF-II transgenic mice, Our f indings demonstrate that moderately increased levels of circulating IG F-II do not cause major changes in skeletal growth and turnover in mic e, This may be due to a lack of activity of circulating IGF-II on bone growth or to physiological consequences of elevated IGF-II, like a re duction of circulating IGF-I or an increase in IGF binding proteins,