Substrain-specific differences in survival and osteonecrosis incidence in a mouse model

Area of Science:

• Immunology
• Genetics
• Pharmacology

Background:

• Previous research identified strain-specific susceptibility to dexamethasone-induced osteonecrosis in mice.
• Dexamethasone is a corticosteroid with known adverse effects, including potential bone complications.

Purpose of the Study:

• To investigate substrain-specific differences in dexamethasone-induced adverse effects between BALB/cJ and BALB/cAnNHsd mice.
• To characterize the susceptibility of these substrains to dexamethasone-induced osteonecrosis.

Main Methods:

• Administration of dexamethasone to BALB/cJ and BALB/cAnNHsd mice at different doses and starting ages.
• Monitoring of mouse weight, mortality, plasma dexamethasone concentrations, and development of osteonecrosis.
• Comparative analysis of adverse effects between the two substrains.

Main Results:

• BALB/cAnNHsd mice weighed more and had lower mortality rates compared to BALB/cJ mice during dexamethasone administration.
• Despite similar plasma dexamethasone concentrations, BALB/cJ mice showed higher susceptibility to osteonecrosis.
• Higher dexamethasone doses and earlier treatment initiation were necessary to induce comparable osteonecrosis frequency in BALB/cAnNHsd mice.

Conclusions:

• This study demonstrates, for the first time, substrain-specific differences in the development of dexamethasone-induced osteonecrosis in mice.
• Genetic background within the BALB/c strain significantly influences susceptibility to corticosteroid-induced bone toxicity.
• These findings highlight the importance of considering substrain variations in preclinical models for drug-induced adverse effects.