Our recent report on a parallel decrease in the
body weights and serum
IGF-I levels of weaver mice suggests that
IGF-I's endocrine function may be impaired in
neurodegenerative diseases. To further understand the overall effects of
IGF-I deficiency on the postnatal growth, we measured bone mineral density (BMD), bone mineral content (BMC), lean body mass (LBM) and fat mass in male and female weaver mice and wild-type littermates on D21 (prepuberty), D45 (puberty), and D60 (postpuberty) using dual-energy X-ray absorptiometry (DEXA). In both male and female weaver mice, we found that the levels of circulating
IGF-I paralleled those of BMD, BMC, and LBM, but not the fat mass. Male weaver mice have normal fat mass at all three ages studied, whereas female weaver mice showed a trend to increase their fat mass as they mature. To determine whether circulating
IGF-I is a determinant of body composition, we crossbred
IGF-I transgenic mice with homozygous weaver mice, which resulted in a significant increase in circulating
IGF-I levels in both male and female weaver mice and normalization of their BMD, BMC and
body weights. In summary, our results demonstrated that normal circulating
IGF-I levels are important in maintaining BMD, BMC, and body composition in
neurodegenerative diseases, such as hereditary
cerebellar ataxia.