IGF-I and postnatal growth of weaver mutant mice

IGF-I is an anabolic growth factor essential for growth and development, both as a mediator of growth hormone (GH) action and as a local stimulator of cell proliferation and differentiation. Although the importance of IGF-I in postnatal growth has been studied for several decades, its functions in pathological states are not fully understood. The weaver (wv) mutant mouse is a commonly used model for studying hereditary cerebellar ataxia and provides us with an opportunity to study the function of IGF-I in postnatal growth during neurodegeneration. In prepubertal wv mice, we found a parallel decrease in body weight and serum IGF-I. This parallel relationship was maintained in females, but not in males, as wv mice entered puberty. Interestingly, we found an increase in the levels of circulating IGF-I and hepatic mRNA preceded the catch-up of body weight of pubertal male wv mice. The increase in IGF-I levels coincided with a surge of circulating androgen at the onset of male puberty, suggesting that androgen might trigger the increase in IGF-I production in the pubertal and adult male wv mice. Overall, our results support the concept that IGF-I plays an important role in postnatal growth during and after neurodegeneration of wv mice. In addition, IGF-I's regulation of systemic growth during and after puberty is likely modulated by androgen in male wv mice.