IGF-I improved bone mineral density and body composition of weaver mutant mice.
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.
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Weiguo
W
Yao
Jin
J
Zhong
Jun
J
Yu
Therry
T
Warner
Tomica
T
Bozic
Ping
P
Ye
A Joseph
AJ
D'Ercole
Janet M
JM
Hock
Wei-Hua
WH
Lee
D000818:Animals; D001823:Body Composition / Q000502:physiology*; D001835:Body Weight / Q000502:physiology*; D015519:Bone Density / Q000502:physiology*; D002524:Cerebellar Ataxia / Q000235:genetics / Q000503:physiopathology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants
D007334:Insulin-Like Growth Factor I