Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Jun;185(3):415-20.
doi: 10.1677/joe.1.06141.

Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences

S Mohan  1 , D J Baylink
Affiliations

Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences

S Mohan et al. J Endocrinol. 2005 Jun.

Abstract

Although it is well established that there is considerable inter-individual variation in the circulating levels of IGF-I in normal, healthy individuals and that a genetic component contributes substantially to this variation, the direct evidence that inter-individual variation in IGF-I contributes to differences in peak bone mineral density (BMD) is lacking. To examine if differences in IGF-I expression could contribute to peak BMD differences, we measured skeletal changes at days 23 (prepubertal), 31 (pubertal) and 56 (postpubertal) in mice with haploinsufficiency of IGF-I (+/-) and corresponding control mice (+/+). Mice (MF1/DBA) heterozygous for the IGF-I knockout allele were bred to generate +/+ and +/- mice (n=18-20 per group). Serum IGF-I was decreased by 23% (P<0.001) in mice with IGF-I haploinsufficiency (+/-) group at day 56 compared with the control (+/+) group. Femoral bone mineral content and BMD, as determined by dual energy X-ray absorptiometry, were reduced by 20% (P<0.001) and 12% respectively in the IGF-I (+/-) group at day 56 compared with the control group. The peripheral quantitative computed tomography measurements at the femoral mid-diaphysis revealed that periosteal circumference (7%, P<0.01) and total volumetric BMD (5%, P<0.05) were decreased significantly in the +/- group compared with the +/+ group. Furthermore, serum IGF-I showed significant positive correlations with both areal BMD (r=0.55) and periosteal circumference (r=0.66) in the pooled data from the +/+ and +/- groups. Our findings that haploinsufficiency of IGF-I caused significant reductions in serum IGF-I level, BMD and bone size, together with the previous findings, are consistent with the notion that genetic variations in IGF-I expression could, in part, contribute to inter-individual differences in peak BMD among a normal population.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

Figures

Figure 1
Figure 1
Serum IGF-I levels in heterozygous IGF-I KO and control mice at 8 weeks of age. Values are means ± S.D. and represent an n of 18–20 per group.
Figure 2
Figure 2
Femur length in heterozygous IGF-I KO and control mice during postnatal growth. Values are means ± S.D. and represent an n of 18–20 per group.
Figure 3
Figure 3
Femoral BMC in heterozygous IGF-I KO and control mice during postnatal growth. Values are means ± S.D. and represent an n of 18–20 per group.
Figure 4
Figure 4
Femur areal BMD in heterozygous IGF-I KO and control mice during postnatal growth. Values are means ± S.D. and represent an n of 18–20 per group.
Figure 5
Figure 5
Femur total vBMD in heterozygous IGF-I KO and control mice during postnatal growth. Values are means ± S.D. and represent an n of 18–20 per group.
Figure 6
Figure 6
Periosteal circumference (Circ.) of the femur in heterozygous IGF-I KO and control mice during postnatal growth. Values are means ± S.D. and represent an n of 18–20 per group.
Figure 7
Figure 7
Correlation between areal BMD of femur and serum levels of IGF-I in heterozygous IGF-I KO and control mice at 8 weeks of age.
Figure 8
Figure 8
Correlation between periosteal circumference of femur and serum levels of IGF-I in heterozygous IGF-I KO and control mice at 8 weeks of age.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Baldock PA, Eisman JA. Genetic determinants of bone mass. Current Opinion in Rheumatology. 2004;16:450–456. - PubMed
    1. Bikle D, Majumdar S, Laib A, Powell-Braxton L, Rosen C, Beamer W, Nauman E, Leary C, Halloran B. The skeletal structure of insulin-like growth factor I-deficient mice. Journal of Bone and Mineral Research. 2001;16:2320–2329. - PubMed
    1. Bikle DD, Sakata T, Leary C, Elalieh H, Ginzinger D, Rosen CJ, Beamer W, Majumdar S, Halloran BP. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone. Journal of Bone and Mineral Research. 2002;17:1570–1578. - PubMed
    1. Bouxsein ML, Rosen CJ, Turner CH, Ackert CL, Shultz KL, Donahue LR, Churchill G, Adamo ML, Powell DR, Turner RT, et al. Generation of a new congenic mouse strain to test the relationships among serum insulin-like growth factor I, bone mineral density, and skeletal morphology in vivo. Journal of Bone and Mineral Research. 2002;17:570–579. - PubMed
    1. Eckstein F, Weusten A, Schmidt C, Wehr U, Wanke R, Rambeck W, Wolf E, Mohan S. Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice. Journal of Bone and Mineral Research. 2004;19:802–810. - PubMed

Publication types

Substances