ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2024
Genetic variation influences the skeletal response to hindlimb unloading in the eight founder strains of the diversity outbred mouse population.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 8 citations in OpenAlex.
- Behavioral and Neurobiological Correlates of Resilience in the Hindlimb Unloading Mouse Model: A Longitudinal Ethogram with Neurotrophin Profile.Life (Basel, Switzerland) · 2026Article
- Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice.Bone reports · 2025Article
- Article
- Genetic Diversity Influences Response and Outcome to Blast Traumatic Brain Injury in a Murine Model.Neurotrauma reportsArticle
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9 authors at 2 institutions in 1 country.
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Abstract
During disuse, mechanical unloading causes extensive bone loss, decreasing bone volume and strength. Variations in bone mass and risk of osteoporosis are influenced by genetics; however, it remains unclear how genetic variation affects the skeletal response to unloading. We previously found that genetic variation affects the musculoskeletal response to 3 weeks of immobilization in the 8 Jackson Laboratory J:DO founder strains: C57Bl/6J, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. Hindlimb unloading (HLU) is the best model for simulating local and systemic contributors of disuse and therefore may have a greater impact on bones than immobilization. We hypothesized that genetic variation would affect the response to HLU across the eight founder strains. Mice of each founder strain were placed in HLU for 3 weeks, and the femurs and tibias were analyzed. There were significant HLU and mouse strain interactions on body weight, femur trabecular BV/TV, and femur ultimate force. This indicates that unloading only caused significant catabolic effects in some mouse strains. C57BL/6 J mice were most affected by unloading while other strains were more protected. There were significant HLU and mouse strain interactions on gene expression of genes encoding bone metabolism genes in the tibia. This indicates that unloading only caused significant effects on bone metabolism genes in some mouse strains. Different mouse strains respond to HLU differently, and this can be explained by genetic differences. These results suggest the outbred J:DO mice will be a powerful model for examining the effects of genetics on the skeletal response to HLU.
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