Disease relevance of Gdf6

• Mice lacking both Gdf5 and Gdf6 show additional defects, including severe reduction or loss of some skeletal elements in the limb, additional fusions between skeletal structures, scoliosis, and altered cartilage in the intervertebral joints of the spinal column [1].
• Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells [2].

High impact information on Gdf6

• GDF5 and the closely related GDF6 and GDF7 define a new subgroup of factors related to known bone- and cartilage-inducing molecules, the bone morphogenetic proteins (BMPs) [3].
• To identify sequences responsible for Gdf6 regulation, we first isolated a series of overlapping bacterial artificial chromosomes (BACs) that extend varying distances upstream and downstream of the gene [4].
• LG16 shares syntenic relationships with mouse chromosome (Mmu) 4, including Gdf6 [5].
• BMP-13 supported chondrogenesis but not terminal differentiation, whereas BMP-2 stimulated endochondral ossification [2].
• The studies show that BMP-13 may fail to support terminal chondrocyte differentiation [2].

Biological context of Gdf6

• In contrast, the other duplicon has retained the intact Uqcrb gene and (in mouse) a copy of the Gdf6 enhancer that has acquired novel mutations [6].
• In mouse and rat, one duplicon now contains a degrading Uqcrb pseudogene but retains strongly conserved sequences within a Gdf6 enhancer [6].

Anatomical context of Gdf6

• Although the biological functions of BMP-13 remain poorly understood, continued postnatal expression of BMP-13 in articular cartilage suggests that this protein may function in an autocrine/paracrine fashion to regulate growth and maintenance of articular cartilage [2].
• When the myoblasts were cultured with BMP-12 or BMP-13, the expression of the myosin heavy chain and the formation of multinucleated myotubes mRNA in L-6 cells [7].

Regulatory relationships of Gdf6

• Unlike BMP-2, neither BMP-12 nor BMP-13 induced alkaline phosphatase activity in C2C12 myoblasts [7].

Analytical, diagnostic and therapeutic context of Gdf6

• Comparative sequence analysis of the Gdf6 locus reveals a duplicon-mediated chromosomal rearrangement in rodents and rapidly diverging coding and regulatory sequences [6].

References