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.
Yao
Weiguo
W
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zhong
Jin
J
Yu
Jun
J
Warner
Therry
T
Bozic
Tomica
T
Ye
Ping
P
D'Ercole
A Joseph
AJ
Hock
Janet M
JM
Lee
Wei-Hua
WH
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