| Autor: |
Alexandra K. O'Donohue, Ya Xiao, Lucinda R. Lee, Timothy Schofield, Tegan L. Cheng, Craig F. Munns, Paul A. Baldock, Aaron Schindeler |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Bone. 167:116636 |
| ISSN: |
8756-3282 |
| DOI: |
10.1016/j.bone.2022.116636 |
| Popis: |
The creation of murine gene knockout models to study bone gene functions often requires the resource intensive crossbreeding of Cre transgenic and gene-floxed strains. The developmental versus postnatal roles of genes can be difficult to discern in such models. For example, embryonic deletion of the Sclerostin (Sost) gene establishes a high-bone mass phenotype in neonatal mice that may impact on future bone growth. To generate a postnatal skeletal knockout of Sost in adult mice, this study used a single injection of a bone-targeted recombinant adeno-associated virus (rAAV) vector.8-week-old SostThe AAV8-Sp7-Cre vector induced widespread persistent recombination in the bone compartment. Regional microCT analyses revealed significant increases in bone with vector treatment. In the L3 vertebrae, SostThis report demonstrates a proof-of-concept that the AAV8-Sp7-Cre vector can efficiently produce postnatal skeletal knockout mice using gene-floxed strains. This technology has the potential for broad utility in the bone field with existing conditional lines. These data also confirm an important postnatal role for Sost in regulating bone homeostasis, consistent with prior studies using neutralizing Sclerostin antibodies, and highlights a novel role of Sost in canalicular remodeling. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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