No rescue of growth deficits by overexpression of IGF-II in IGF-I deficient mice

IGF-I and IGF-II are single-chain peptides produced by many tissues and function in an autocrine/paracrine fashion. They are involved in the regulation of cell growth, differentiation, metabolism and death. Despite their structural similarity and common origin, each growth factor has its own expression pattern and specific functions. IGF-I is necessary for normal growth and differentiation during both the embryonic and the postnatal periods. IGF-II is an essential stimulator of fetal growth, but its function in the postnatal period is unclear. Notably, expression of IGF-II is shut down shortly after birth in rodents (but not in humans). An interesting observation is the frequent overexpression of IGF-II in a variety of human malignancies. Overexpression of IGF-II in transgenic mice resulted in disproportionate growth of specific organs and, in some cases, in increased tumor formation. However, a significant increase in body size was not observed. The aim of this study was to test whether elevated levels of circulating IGF-II can rescue the dwarfism of IGF-I deficient mice and thereby function as a stimulator of postnatal growth in the absence of IGF-I.

Igf1+/– mice were crossed with Igf1+/– mice carrying PEPCK-IGF-II transgenes. The genotype of the offspring was determined by PCR. Body weight was recorded daily until the age of 8 weeks, when the animals were killed by exsanguination under anesthesia. The nose-rump length (NRL) and the weights of individual organs and of carcass were measured. Size and mineral density of femur and first lumbar vertebra were determined.

Serum IGF-II levels of IGF-II transgenic Igf1–/– mice (231±37 ng/ml, n=4) were significantly higher than in Igf1–/– mice lacking the IGF-II transgene (26±3.2 ng/ml, n=5). Nevertheless, body weight, NRL and the bone parameters investigated were not different between these two groups. The weight of specific organs, however, was altered. In summary, under our experimental conditions, IGF-II was not able to rescue the postnatal growth deficit of Igf1–/– mice.