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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
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Mesoderm-specific Stat3 deletion affects expression of Sox9 yielding Sox9-dependent phenotypes
Michael D Hall1, Caroline A Murray1, Michael J Valdez1
1The Cancer and Developmental Biology Laboratory, National Cancer Institute-Frederick, Frederick, Maryland, United States of America.
Plos Genetics
|February 7, 2017
Summary
Signal transducer and activator of transcription 3 (Stat3) is crucial for normal SOX9 gene expression in developing cartilage. Loss of Stat3 in mice causes skeletal defects and dwarfism, mimicking human campomelic dysplasia.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Campomelic dysplasia (CD) is primarily caused by SOX9 gene mutations or translocations.
- Mechanisms regulating normal SOX9 expression and related signaling pathways are not fully understood.
- Understanding SOX9 regulation is key to addressing CD pathogenesis.
Purpose of the Study:
- To identify novel regulators of SOX9 expression.
- To elucidate the role of these regulators in skeletal development and CD.
- To explore potential therapeutic targets for campomelic dysplasia.
Main Methods:
- Conditional ablation of Stat3 in mesodermal tissues using TCre.
- Conditional deletion of Stat3 using a Sox9Cre driver.
- In vivo and ex vivo mechanistic studies to assess SOX9 expression and Stat3 binding.
Main Results:
- Conditional Stat3 ablation in mesoderm leads to dwarfism and skeletal defects resembling CD.
- Stat3 loss causes growth plate abnormalities and deregulated endochondral ossification.
- Stat3 directly activates SOX9 expression by binding to its promoter.
Conclusions:
- Stat3 is a key modulator of SOX9 expression in chondrocytes during skeletal development.
- Stat3 plays a critical role in endochondral ossification and skeletal patterning.
- Targeting Stat3 offers a potential therapeutic strategy for campomelic dysplasia.
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