Overexpression of IGF‐I transgene rescued growth retardation of weaver mutant mice

Abstract

IGF-I is an important growth factor for postnatal growth in mammals. To evaluate the relative contribution of IGF-1 in postnatal growth during pathological states, we used weaver mutant mouse. We found that, compared with their control littermates, the body weights of both male and female weaver (wv) mice were significantly decreased soon after birth and remained low later in life, although male wv mice showed a trend to catch-up to normal growth. Organ weights of wv mice also showed a proportional decrease. To determine if the growth retardation in wv mice is related to IGF-I deficiency, we measured circulating IGF-I levels by radioimmunoassay and hepatic IGF-I mRNA levels by Northern blot. Out data showed a parallel decrease of IGF-I and body weights in female and D21 male wv mice. After male wv mice entered puberty, their IGF-I levels caught-up to that of their wildtype littermates as well as their body weight. These data suggested that IGF-I deficiency may be the cause of postnatal growth retardation in wv mutant mice. After crossbred wv mice with IGF-I transgenic mice, wv mice carrying the IGF-I transgene restored their body weights to those of their wildtype littermates. Interestingly, among other organs, only brain, spleen and female liver showed significant weight increases. In summary, we demonstrated that the decrease in circulating IGF-I contributed to postnatal growth retardation in wv mutant mice, which was confirmed by the nearly normal growth pattern of wv mice in the presence of IGF-I transgene. Overall, our results support the notion that IGF-I plays an important role in postnatal growth in normal as well as neurodegenerative states.