Differences in bone structure and unloading-induced bone loss between C57BL/6N and C57BL/6J mice

Abstract

The C57BL/6 mouse, the most frequently utilized animal model in biomedical research, is in use as several substrains, all of which differ by a small array of genomic differences. Two of these substrains, C57BL/6J (B6J) and C57BL/6N (B6N), are commonly used but it is unclear how phenotypically similar or different they are. Here, we tested whether adolescent B6N mice have a bone phenotype and respond to the loss of weightbearing differently than B6J. At 9 weeks of age, normally ambulating B6N had lower trabecular bone volume fraction but greater bone formation rates and osteoblast surfaces than corresponding B6J. At 11 weeks of age, differences in trabecular indices persisted between the substrains but differences in cellular activity had ceased. Cortical bone indices were largely similar between the two substrains. Hindlimb unloading (HLU) induced similar degeneration of trabecular architecture and cellular activity in both substrains when comparing 11-week-old HLU mice to 11-week-old controls. However, unloaded B6N mice had smaller cortices than B6J. When comparing HLU to 9 weeks baseline control mice, deterioration in trabecular separation, osteoblast indices, and endocortical variables was significantly greater in B6N than B6J. These data indicate specific developmental differences in bone formation and morphology between B6N and B6J mice, giving rise to a differential response to mechanical unloading that may be modulated, in part, by the genes Herc2, Myo18b, and Acan. Our results emphasize that these substrains cannot be used interchangeably at least for investigations in which the phenotypic makeup and its response to extraneous stimuli are of interest.

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors

“…We speculate that ovariectomy induced bone loss recapitulates age‐related trabecular bone deterioration patterns, reported to be more severe in the metaphyseal region of the long bones than the vertebral body in C57BL/6J mice . These results are consistent with those reported previously . To examine the mechanism, we looked at OB and OC by histology.…”

“…22 These results are consistent with those reported previously. 60,61 To examine the mechanism, we looked at OB and OC by histology. Our finding of increased OB and decreased OC in the proximal tibia or L6 spine of MRL/MpJ mice compared to C57BL/6J mice indicates that MRL/MpJ mice are able to maintain bone mass by a mechanism of accelerated bone formation and reduced bone resorption during osteoporosis development following ovariectomy surgery.…”

Influence of Social Isolation During Prolonged Simulated Weightlessness by Hindlimb Unloading

“…We then performed a 30-day HU study under these social housing conditions, side-by-side with animals maintained according to the standard NASA single housing HU system (Figure 1). Animals selected for this study were female C57BL/6NJ mice shown previously to be sensitive to bone loss caused by HU (Sankaran et al, 2017). Controls (normally loaded, NL) were age- and sex-matched animals freely ambulating in standard mouse cages.…”

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

“…Previous studies show cancellous bone loss begins in early adulthood in C57BL/6 mice (2-3month-old), earlier than that of BMD 23,24,46 . Notably, different mouse strains exhibit different patterns in bone loss [47][48][49] . C57BL/ 6J mice experience bone loss as early as 2 months of age, while BALB/c mice wouldn't show significant reduction until 7 months 50 .…”