Congenic Mice Provide in Vivo Evidence for a Genetic Locus that Modulates Serum Insulin-Like Growth Factor-I and Bone Acquisition
Copyright policy )Congenic Mice Provide in Vivo Evidence for a Genetic Locus that Modulates Serum Insulin-Like Growth Factor-I and Bone Acquisition
We identified quantitative trait loci (QTL) that determined the genetic variance in serum IGF-I through genome-wide scanning of mice derived from C57BL/6J(B6) × C3H/HeJ(C3H) intercrosses. One QTL (Igf1s2), on mouse chromosome 10 (Chr10), produces a 15% increase in serum IGF-I in B6C3 F2 mice carrying c3 alleles at that position. We constructed a congenic mouse, B6.C3H-10 (10T), by backcrossing c3 alleles from this 57-Mb region into B6 for 10 generations. 10T mice have higher serum and skeletal IGF-I, greater trabecular bone volume fraction, more trabeculae, and a higher number of osteoclasts at 16 wk, compared with B6 (P < 0.05). Nested congenic sublines generated from further backcrossing of 10T allowed for recombination and produced four smaller sublines with significantly increased serum IGF-I at 16 wk (i.e. 10-4, 10-7, 10-10, and 10-13), compared with B6 (P < 0.0003), and three smaller sublines that showed no differences in IGF-I vs. age- and gender-matched B6 mice. Like 10T, the 10-4 nested sublines at 16 wk had higher femoral mineral (P < 0.0001) and greater trabecular connectivity density with significantly more trabeculae than B6 (P < 0.01). Thus, by comprehensive phenotyping, we were able to narrow the QTL to an 18.3-Mb region containing approximately 148 genes, including Igf1 and Elk-3(ETS domain protein). Allelic differences in the Igf1s2 QTL produce a phenotype characterized by increased serum IGF-I and greater peak bone density. Congenic mice establish proof of concept of shared genetic determinants for both circulating IGF-I and bone acquisition.
- The University of Texas at Austin United States
- University of Connecticut United States
- Jackson Laboratory United States
Body-Composition, Bone-Marrow-Cells, Male, Chromosomes-Mammalian, Gene-Expression, 610, Gene Expression, Bone Marrow Cells, Mice, Mice, Congenic, Bone Density, Animals, Bone-Density, Femur, Mice-Inbred-C3H, Insulin-Like Growth Factor I, Cells, Cultured, Mice, Inbred C3H, Mice-Inbred-C57BL, Mice-Congenic, Chromosome Mapping, Chromosomes, Mammalian, Bone-Remodeling, Mice, Inbred C57BL, Phenotype, Liver, Cells-Cultured, Chromosome-Mapping, Insulin-Like-Growth-Factor-I, Body Composition, Female, Bone Remodeling, Stromal Cells, Stromal-Cells
Body-Composition, Bone-Marrow-Cells, Male, Chromosomes-Mammalian, Gene-Expression, 610, Gene Expression, Bone Marrow Cells, Mice, Mice, Congenic, Bone Density, Animals, Bone-Density, Femur, Mice-Inbred-C3H, Insulin-Like Growth Factor I, Cells, Cultured, Mice, Inbred C3H, Mice-Inbred-C57BL, Mice-Congenic, Chromosome Mapping, Chromosomes, Mammalian, Bone-Remodeling, Mice, Inbred C57BL, Phenotype, Liver, Cells-Cultured, Chromosome-Mapping, Insulin-Like-Growth-Factor-I, Body Composition, Female, Bone Remodeling, Stromal Cells, Stromal-Cells
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).42 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!