Circulating and skeletal insulin-like growth factor-I (IGF-i) concentrations in two inbred strains of mice with different bone mineral densities

Rosen, Clifford J.; Dimai, Hans-Peter; Vereault, Donald; Donahue, Leah Rae; Beamer, Wesley G.; Farley, John R.; Linkhart, Susan G.; Linkhart, Thomas A.; Mohan, Subburaman; Baylink, David J.

doi:10.1016/s8756-3282(97)00143-9

Cited by 151 publications

(94 citation statements)

References 18 publications

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“…They were maintained under conditions of 14 h light:10 h darkness and an ambient temperature of 20·2 C. Water (acidified with HCl, pH 2·8-3·2) and an autoclaved NIH31 pellet diet (18% protein, 6% fat, 1·27% Ca, 0·92% P, trace mineral and vitamin fortified; Purina, Madison, WI, USA) were freely available. The body weights of B6 and C3H were not different, as described previously (Rosen et al 1997). We previously reported that serum IGF-I concentrations as measured by a specific RIA were 30% higher in C3H than B6 at 4 and 8 weeks in both male and female mice (Rosen et al 1997).…”

Section: Animalssupporting

confidence: 78%

“…The body weights of B6 and C3H were not different, as described previously (Rosen et al 1997). We previously reported that serum IGF-I concentrations as measured by a specific RIA were 30% higher in C3H than B6 at 4 and 8 weeks in both male and female mice (Rosen et al 1997). The mice were killed at 8 weeks and pituitary gland, liver, skeletal muscle (quadriceps femoris) from B6 and C3H (n=10/group) were collected and flash-frozen in liquid nitrogen and then stored at 80 C for subsequent mRNA analysis.…”

Section: Animalsmentioning

confidence: 97%

“…Serum IGF-I in mouse sera was measured by RIA after removal of IGF-binding proteins as described previously (Rosen et al 1997).…”

Section: Serum Igf-i Measurementsmentioning

confidence: 99%

“…Furthermore, only a modest growth retardation was observed in LID mice despite their having an extremely low level of serum IGF-I (Yakar et al 2002), suggesting that the serum IGF-I level is not a critical determinant of body growth. Therefore, it is not surprising that the body weight and height of B6 and C3H are identical, despite having different levels of serum IGF-I (Rosen et al 1997). Interestingly, LID mice demonstrated muscle insulin resistance with high serum insulin concentration (Yakar et al 2001), hypercholesterolemia and reduced cortical periosteal bone growth (Sjogren et al 2002).…”

Section: Figurementioning

confidence: 99%

“…C3H/HeJ (hereafter C3H) mice have 30% higher serum IGF-I concentrations than C57BL/6J (hereafter B6) mice although there are no differences in body length and weight between the two strains (Rosen et al 1997). C3H mice with higher serum IGF-I levels have increased BMD compared with B6.…”

Section: Introductionmentioning

confidence: 99%

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Genetic differences in the IGF-I gene among inbred strains of mice with different serum IGF-I levels

Iida¹,

Rosen²,

Ackert‐Bicknell³

et al. 2005

Journal of Endocrinology

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There is significant heterogeneity in serum IGF-I concentrations among normal healthy individuals across all ages and among inbred strains of mice. C3H/HeJ (C3H) mice have 30% higher serum IGF-I concentrations over a lifetime than C57BL/6J (B6), even though body size and length are identical. The underlying mechanism for this disparity remains unknown although several possibilities exist including altered GH secretion, resistance to GH action, or impaired IGF-I secretion from the liver or peripheral tissues. To study this further, we evaluated mRNA levels of pituitary GH, and of IGF-I, GH receptor (GHR) and acid-labile subunit (ALS) in liver and skeletal muscle of male C3H and B6 strains. mRNA levels of hepatic IGF-I paralleled serum IGF-I levels, whereas pituitary GH mRNA expression was significantly lower in C3H than B6. In addition, reduced hepatic mRNA levels of ALS and GHR in B6 suggests hepatic GH resistance in B6. In contrast, mRNA levels of IGF-I and GHR in skeletal muscle were not different between B6 and C3H. There was a single sequence repeat polymorphism (SSR) in the promoter region of both GHR and IGF-I genes in mice; the SSR in the IGF-I gene was significantly different between the two strains. The SSR in the IGF-I gene corresponds to the E2F binding site, which is critical for regulating IGF-I gene expression. These results suggest that the SSR in the promoter region of the IGF-I gene may be partially responsible for differences in serum IGF-I levels between B6 and C3H strains.

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Section: Animalssupporting

confidence: 78%

Section: Animalsmentioning

confidence: 97%

“…Serum IGF-I in mouse sera was measured by RIA after removal of IGF-binding proteins as described previously (Rosen et al 1997).…”

Section: Serum Igf-i Measurementsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Genetic differences in the IGF-I gene among inbred strains of mice with different serum IGF-I levels

Iida¹,

Rosen²,

Ackert‐Bicknell³

et al. 2005

Journal of Endocrinology

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Bone density phenotypes in mice aneuploid for the Down syndrome critical region

Olson

Mohan

2011

American J of Med Genetics Pt A

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Down syndrome (trisomy 21) is associated with reduced bone density in humans, but it is unclear whether this is due to specific effects of chromosome 21 genes or lifestyle factors. Mouse models with aneuploidy of segments of mouse chromosome 16 that are homologous to human chromosome 21 can be used to elucidate the mechanism by which Down syndrome phenotypes arise. Ts1Rhr and Ms1Rhr mice are trisomic and monosomic, respectively, for the hypothesized "Down syndrome critical region" containing approximately 33 genes. We assessed the skeletons of these mice from 3 to 16 weeks of age using dual X-ray absorptiometry. Ts1Rhr mice were unexpectedly similar to normal controls, showing that a larger region of trisomy is necessary to recapitulate the Down syndrome phenotype. Ms1Rhr mice, in contrast, showed decreases in weight, bone mineral content, bone mineral density, and bone area from weaning to adulthood. Regional bone density was also decreased in the femur, tibia, and lower lumbar spine. The microarchitecture of 3 week old Ms1Rhr femurs was then analyzed using µCT. Volumetric density, total tissue volume, bone volume, and bone fraction were all reduced in both cortical and trabecular bone. Ms1Rhr trabeculae were thinner and had decreased connectivity. A 31.5% reduction in the level of insulin-like growth factor I in the serum was found, and we hypothesize that this is responsible for the bone density phenotype. We discuss bone-related genes in the region and propose that humans with distal chromosome 21 deletions may exhibit reduced bone density.

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IGF-1 and bone: New discoveries from mouse models

Yakar¹,

Courtland²,

Clemmons³

2010

Journal of Bone and Mineral Research

121

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Insulin-like growth factor-1 (IGF-1) plays a central role in cellular growth, differentiation, survival, and cell cycle progression. It is expressed early during development and its effects are mediated through binding to a tyrosine kinase receptor, the insulin-like growth factor-1 receptor (IGF-1R). In the circulation, the IGFs bind to IGF-binding proteins (IGFBPs), which determine their bioavailability and regulate the interaction between the IGFs and IGF-1R. Studies in animal models and in humans have established critical roles for IGFs in skeletal growth and development. In this review we present new and old findings from mouse models of the IGF system and discuss their clinical relevance to normal and pathological skeletal physiology. © 2010 American Society for Bone and Mineral Research.

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Circulating and skeletal insulin-like growth factor-I (IGF-i) concentrations in two inbred strains of mice with different bone mineral densities

Cited by 151 publications

References 18 publications

Genetic differences in the IGF-I gene among inbred strains of mice with different serum IGF-I levels

Genetic differences in the IGF-I gene among inbred strains of mice with different serum IGF-I levels

Bone density phenotypes in mice aneuploid for the Down syndrome critical region

IGF-1 and bone: New discoveries from mouse models

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