Supported by USDA-TSTAR (2008-34135-19322) and NIH (5P20RR024206-01A1).
Transgenic over-expression of growth differentiation factor 11 propeptide in skeleton results in transformation of the seventh cervical vertebra into a thoracic vertebra†
Article first published online: 3 NOV 2010
Copyright © 2010 Wiley-Liss, Inc.
Molecular Reproduction and Development
Volume 77, Issue 11, pages 990–997, November 2010
How to Cite
Li, Z., Kawasumi, M., Zhao, B., Moisyadi, S. and Yang, J. (2010), Transgenic over-expression of growth differentiation factor 11 propeptide in skeleton results in transformation of the seventh cervical vertebra into a thoracic vertebra. Mol. Reprod. Dev., 77: 990–997. doi: 10.1002/mrd.21252
- Issue published online: 20 NOV 2010
- Article first published online: 3 NOV 2010
- Accepted manuscript online: 6 OCT 2010 11:29AM EST
- Manuscript Accepted: 21 SEP 2010
- Manuscript Received: 22 JUL 2010
- USDA-TSTAR Programs. Grant Number: 2008-34135-19322
- NIH COBRE Grant. Grant Number: 5P20RR024206-01A1
Growth differentiation factor 11 (GDF11) is one of the significant genes that control skeletal formation. Knockout of GDF11 function causes abnormal patterning of the anterior/posterior axial skeleton. The mRNA of GDF11 is initially translated to a precursor protein that undergoes a proteolytic cleavage to generate the C-terminal peptide or mature GDF11, and the N-terminal peptide named GDF11 propeptide. The propeptide can antagonize GDF11 activity in vitro. To investigate the effects of GDF11 propeptide on GDF11 function in vivo, we generated transgenic mice that over-express the propeptide cDNA in skeletal tissue. The transgenic mice showed formation of extra ribs on the seventh cervical vertebra (C7) as a result of transformation of the C7 vertebra into a thoracic vertebra. The GDF11 propeptide transgene mRNA was detected in tail tissue in embryos and was highly expressed in tail and calvaria bones after birth. A high frequency of C7 rib formation was noticed in the transgenic mouse line with a high level of transgene expression. The anterior boundaries of Hoxa-4 and Hoxa-5 mRNA in situ expressions showed cranial shifts from their normal prevertebra locations in transgenic embryos. These results demonstrated significant effects of GDF11 propeptide transgene on vertebral formation, which are likely occurring through depressing GDF11 function and altered locations of Hoxa-4 and Hoxa-5 expression. Mol. Reprod. Dev. 77:990–997, 2010. © 2010 Wiley-Liss, Inc.