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Open Access Substrain-Specific Differences in Survival and Osteonecrosis Incidence in a Mouse Model

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Abstract:

We previously reported strain-specific susceptibility to dexamethasone-induced osteonecrosis in mice. Here we report that BALB/cJ and BALB/cAnNHsd mice display substrain-specific differences in dexamethasone-induced adverse effects. As compared with BALB/cJ mice, BALB/cAnNHsd weighed more (16.6 g compared with 13.7 g) at the beginning of dexamethasone administration on postnatal day 28 and fewer died during the dexamethasone regimen (10% compared with 50%). Although the 2 substrains had similar plasma concentrations of dexamethasone, BALB/cJ mice were more susceptible to developing dexamethasone-induced osteonecrosis. A higher dose of dexamethasone (8 mg/L) throughout the treatment period compared with a lower dose (8 mg/L loading dose during week 1 followed by 4 mg/L for the remainder of the treatment period) and earlier start of treatment (postnatal day 24 compared with postnatal day 28) was required to induce osteonecrosis with a similar frequency in BALB/cAnNHsd mice as in BALB/cJ mice. Our results show, for the first time, substrain-specific differences in the development of osteonecrosis in mice.

Document Type: Research Article

Affiliations: 1: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Pharmacy Pharmacology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2: Department of Veterinary Pathology Core, St Jude Children's Research Hospital, Memphis, Tennessee, USA 3: Department of Animal Resource Center (Veterinary Services), St Jude Children's Research Hospital, Memphis, Tennessee, USA 4: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA 5: Department of Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA 6: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA. mary.relling@stjude.org

Publication date: December 1, 2012

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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