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Related Experiment Videos

Genetics and bone. Using the mouse to understand man.

W G Beamer1, L R Donahue, C J Rosen

  • 1The Jackson Laboratory, Bar Harbor, ME 04609, USA. wgb@aretha.jax.org

Journal of Musculoskeletal & Neuronal Interactions
|March 11, 2005
PubMed
Summary
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Inbred mouse strains reveal genetic factors influencing bone mineral density (BMD). Specific genes on multiple chromosomes affect femoral and vertebral BMD, with implications for skeletal research and understanding bone diseases.

Area of Science:

  • Genetics and Genomics
  • Skeletal Biology
  • Animal Models

Background:

  • Inbred mouse strains are valuable tools in bone research due to practical advantages and established genetic methodologies.
  • Significant variations in femoral and vertebral bone mineral density (BMD) exist between different inbred mouse strains, such as C57BL/6J (low BMD) and C3H/HeJ (high BMD).
  • Understanding the genetic basis of BMD diversity is crucial for advancing skeletal research.

Purpose of the Study:

  • To identify quantitative trait loci (QTLs) associated with variations in femoral and vertebral bone mineral density (BMD) in mice.
  • To investigate the inheritance patterns of BMD and other skeletal phenotypes.
  • To validate identified BMD QTLs using congenic mouse strains.

Main Methods:

  • Crossbreeding of C57BL/6J and C3H/HeJ mice to generate an F2 intercross population (B6C3F2).

Related Experiment Videos

  • Genotyping of 1000 F2 female mice for PCR product polymorphisms across all 19 autosomes.
  • Genome-wide analysis for genotype-phenotype correlations to identify BMD QTLs.
  • Creation of congenic mouse strains by backcrossing C3H QTL regions onto the B6 background for QTL verification.
  • Phenotyping of bone mineral density, geometry, strength, and serum markers.

    • Main Results:

    • Genome-wide analyses identified QTLs for femoral BMD on 10 chromosomes and for vertebral BMD on 7 chromosomes.
    • LOD scores ranged from 2.90 to 24.4, accounting for 1-10% of the F2 variance.
    • Both dominant-recessive and additive inheritance patterns were observed, with progenitor strains contributing alleles affecting BMD.
    • Congenic strains confirmed that specific QTL regions significantly altered femoral BMD as predicted.
    • Gender-specific effects on BMD QTLs and over 30 additional skeletal phenotypes were identified.

    Conclusions:

    • Multiple QTLs on various chromosomes significantly influence femoral and vertebral BMD in mice, with complex inheritance patterns.
    • The study successfully validated BMD QTLs using congenic strains, demonstrating their impact on bone density.
    • These findings provide valuable genetic insights into BMD regulation and skeletal diversity, applicable to bone research and disease.