133
Views
24
CrossRef citations to date
0
Altmetric
Research Article

BMP Regulation of the Mouse Connexin43 Promoter in Osteoblastic Cells and Embryos

, , , , &
Pages 37-50 | Published online: 11 Jul 2009
 

Abstract

We examined BMP regulation of the gap junction gene Gjal (Cx43 &#102 1) using a series of lacZ reporter constructs containing up to 6.7 kbs of mouse Cx43 &#102 1 promoter sequence. Using transient transfection assays, we showed that BMP2, BMP4, and GDF5, but not BMP6 or BMP7, can modulate Cx43 &#102 1 promoter activity in the osteosarcoma cell line ROS17/2.8. Positive regulatory elements were found at the proximal and distal ends of the 6.7 kb promoter fragment, while negative regulatory elements were found in the intervening region. Comparison of Cx43 &#102 1 promoter sequences from the human vs. mouse showed five regions with significant sequence conservation, two of which contained Smad binding elements in conjunction with a BMP response element. Analysis of a transgenic mouse line containing a Cx43 &#102 1 promoter driven lacZ reporter construct revealed lacZ expression in the developing joints, an expression pattern similar to that previously reported for Gdf5. LacZ expression was also observed in axial regions of the skeletal anlage, which in situ hybridization analysis confirmed as sites of Gdf5 transcript expression. When the Cx43 &#102 1 promoter driven lacZ transgene was bred into the brachypodism mouse Gdf5 bpJ ( bp ) harboring a Gdf5 loss of function mutation, lacZ expression was extinguished. This was observed in homozygous and heterozygous bp animals, suggesting that Cx43 &#102 1 promoter regulation by GDF5 is subject to haploinsufficiency. Overall, these observations are consistent with recent studies by others indicating a role for Cx43 &#102 1 in osteogenesis and osteoblastic function during mouse development.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.