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Intramembranous bone regeneration in diversity outbred mice is heritable
Meghan M Moran1, Frank C Ko1, Larry D Mesner2
1Department of Anatomy & Cell Biology, Rush University Medical Center, Chicago, IL, USA; Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, USA.
Bone
|August 26, 2022
Summary
Diversity Outbred (DO) mice show significant genetic variability and heritability in bone regeneration, making them a suitable model for future genetic studies of bone repair. This research aids in understanding the genetic basis of bone healing.
Area of Science:
- Orthopedics
- Genetics
- Regenerative Medicine
Background:
- Failed bone repair affects over a million individuals annually in the U.S., causing significant morbidity and costs.
- Genome-wide association studies (GWAS) have identified genes for bone traits, but applying this to human bone repair is challenging.
- A genetically diverse model organism is needed to study the genetic factors influencing bone repair.
Purpose of the Study:
- To evaluate the phenotypic distribution, sex effects, and heritability of intramembranous bone regeneration in Diversity Outbred (DO) mice.
- To determine if DO mice are a suitable model for genetic studies on bone repair using GWAS.
- To assess the correlation between bone regeneration and intact bone mass.
Main Methods:
- Femoral marrow ablation was performed on 47 12-week-old DO mice (23 males, 24 females).
- Bone regeneration was assessed on day 7 post-ablation.
- Phenotypic variation, heritability, sex effects, and correlations with intact bone mass were analyzed.
Main Results:
- DO mice exhibited substantial variability (CV 86%) and heritability (0.42) in bone regeneration, comparable to inbred strains.
- A trend towards greater bone regeneration was observed in males compared to females.
- Bone regeneration showed weak or no correlation with intact bone mass, suggesting independent genetic factors.
Conclusions:
- DO mice demonstrate sufficient variation and heritability in intramembranous bone regeneration.
- This genetic diversity makes DO mice a promising model for future GWAS to identify genes controlling bone repair.
- The findings suggest that genetic factors for bone regeneration and intact bone mass are at least partially independent.
