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Gene Review

Gdf5  -  growth differentiation factor 5

Mus musculus

Synonyms: BMP-14, Bmp14, Bone morphogenetic protein 14, Bp, CDMP-1, ...
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Disease relevance of Gdf5

  • 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].
  • CONCLUSIONS: The localization of transcripts for BMP-4, -6, and GDF-5 as well as BMP receptors shown during the present experimental model indicate the possible involvement of molecular signaling by these BMPs in the chondrogenic progress in spondylosis [2].
  • Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy [3].
  • Structurally, GDF-5-deficient femora were weaker (-31%) and more compliant (-57%) than controls when tested to failure in torsion [4].
  • Using a 509 bp probe from the 5' region of pet, 10 cosmid clones of an E. coli CFT073 gene library were positive for hybridization [5].

High impact information on Gdf5

  • The homeo box is a 180 bp protein-coding domain found within homeotic genes of Drosophila and conserved in a variety of invertebrate and vertebrate species [6].
  • We now report the isolation of three new members of the transforming growth factor-beta (TGF-beta) superfamily (growth/differentiation factors (GDF) 5,6 and 7) and show by mapping, expression patterns and sequencing that mutations in Gdf5 are responsible for skeletal alterations in bp mice [7].
  • These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord [3].
  • Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation [3].
  • The intron is flanked by two 9 bp direct repeats, revealing the acquisition by insertion of a novel rRNA processing strategy in the evolution of higher organisms [8].

Biological context of Gdf5


Anatomical context of Gdf5

  • Overactivity of Bmp4 in the skeleton caused an increase of cartilage production and enhanced chondrocyte differentiation, as GDF5 expression did, but it did not disturb joint formation as GDF5 did [14].
  • Previous work using the brachypod mouse has suggested that GDF-5 affects Achilles tendon composition, ultrastructure, and material behavior, as well as tendon repair [15].
  • Mice deficient in GDF-5 have also been shown to exhibit biomechanical abnormalities in tendon that may be associated with altered type I collagen [4].
  • CONCLUSION: The intervertebral disc is markedly affected by GDF-5 deficiency [16].
  • The results shown here demonstrate concordance between the mRNA expression profiles of GDF5 and the gap junction gene, Cx43, in the mouse embryonic limb, spine, and heart, consistent with coordinated functions for these gene products during developmental organogenesis [17].

Associations of Gdf5 with chemical compounds


Physical interactions of Gdf5


Regulatory relationships of Gdf5

  • We show that this change in role of Bapx1 following the transition to the mammalian ossicle configuration is not due to a change in expression pattern but results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be essential in joint formation [24].
  • Quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) results show that GDF-5 was upregulated two-threefold in response to the absence of GDF-7 protein [15].
  • Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells [25].

Other interactions of Gdf5

  • Mice carrying null mutations in both Gdf5 and another BMP family member, Bmp5, show additional abnormalities not observed in either of the single mutants [26].
  • Together with the common effect on the cartilage overproduction by Bmp4 and GDF5 overactivation, loss of cartilage by inactivation of multiple BMPs in Noggin transgenic mice indicates that signals for cartilage production are reinforced by multiple BMPs exclusively [14].
  • Scleraxis mRNA level was reduced by CDMP treatment [12].
  • No GDF-5 and BMP-6 mRNA was detected at this stage [2].
  • The mouse brachypodism locus encodes a bone morphogenetic protein (BMP)-like molecule called growth/differentiation factor 5 (GDF5) [26].

Analytical, diagnostic and therapeutic context of Gdf5

  • In situ hybridization in bp mice showed overexpression of Gdf5 mRNA in the developing phalanges where apoptotic cells were increased [27].
  • Northern blot analysis showed that an mRNA encoding for beta Bp is present in the Philly mouse lens, but normal beta Bp could not be detected [28].
  • Western blot analysis with antibodies against specific beta Bp peptide sequences showed that the Philly protein shares the same amino-terminal residue as beta Bp but lacks a part of the carboxyl-terminal half of normal beta Bp [28].
  • The altered protein is slightly smaller than beta Bp and has a more acidic isoelectric point by two-dimensional gel electrophoresis [28].
  • One highly transformed colony arising in the infected NIH3T3 cell culture contained a provirus with a 1900 bp cDNA insert [29].


  1. Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Settle, S.H., Rountree, R.B., Sinha, A., Thacker, A., Higgins, K., Kingsley, D.M. Dev. Biol. (2003) [Pubmed]
  2. Distribution of genes for bone morphogenetic protein-4, -6, growth differentiation factor-5, and bone morphogenetic protein receptors in the process of experimental spondylosis in mice. Nakase, T., Ariga, K., Miyamoto, S., Okuda, S., Tomita, T., Iwasaki, M., Yonenobu, K., Yoshikawa, H. J. Neurosurg. (2001) [Pubmed]
  3. Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation. Tsumaki, N., Tanaka, K., Arikawa-Hirasawa, E., Nakase, T., Kimura, T., Thomas, J.T., Ochi, T., Luyten, F.P., Yamada, Y. J. Cell Biol. (1999) [Pubmed]
  4. The effect of growth/differentiation factor-5 deficiency on femoral composition and mechanical behavior in mice. Mikic, B., Battaglia, T.C., Taylor, E.A., Clark, R.T. Bone (2002) [Pubmed]
  5. Identification of sat, an autotransporter toxin produced by uropathogenic Escherichia coli. Guyer, D.M., Henderson, I.R., Nataro, J.P., Mobley, H.L. Mol. Microbiol. (2000) [Pubmed]
  6. Homeo box gene complex on mouse chromosome 11: molecular cloning, expression in embryogenesis, and homology to a human homeo box locus. Hart, C.P., Awgulewitsch, A., Fainsod, A., McGinnis, W., Ruddle, F.H. Cell (1985) [Pubmed]
  7. Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Storm, E.E., Huynh, T.V., Copeland, N.G., Jenkins, N.A., Kingsley, D.M., Lee, S.J. Nature (1994) [Pubmed]
  8. Novel processing in a mammalian nuclear 28S pre-rRNA: tissue-specific elimination of an 'intron' bearing a hidden break site. Melen, G.J., Pesce, C.G., Rossi, M.S., Kornblihtt, A.R. EMBO J. (1999) [Pubmed]
  9. BMP receptor signaling is required for postnatal maintenance of articular cartilage. Rountree, R.B., Schoor, M., Chen, H., Marks, M.E., Harley, V., Mishina, Y., Kingsley, D.M. PLoS Biol. (2004) [Pubmed]
  10. Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity. Baur, S.T., Mai, J.J., Dymecki, S.M. Development (2000) [Pubmed]
  11. Cloning, expression profile, and genomic organization of the mouse STAP/A170 gene. Okazaki, M., Ito, S., Kawakita, K., Takeshita, S., Kawai, S., Makishima, F., Oda, H., Kakinuma, A. Genomics (1999) [Pubmed]
  12. Cartilage-derived morphogenetic proteins induce osteogenic gene expression in the C2C12 mesenchymal cell line. Yeh, L.C., Tsai, A.D., Lee, J.C. J. Cell. Biochem. (2005) [Pubmed]
  13. Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis. Hatakeyama, Y., Tuan, R.S., Shum, L. J. Cell. Biochem. (2004) [Pubmed]
  14. Bone morphogenetic protein signals are required for cartilage formation and differently regulate joint development during skeletogenesis. Tsumaki, N., Nakase, T., Miyaji, T., Kakiuchi, M., Kimura, T., Ochi, T., Yoshikawa, H. J. Bone Miner. Res. (2002) [Pubmed]
  15. Achilles tendon characterization in GDF-7 deficient mice. Mikic, B., Bierwert, L., Tsou, D. J. Orthop. Res. (2006) [Pubmed]
  16. Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular changes when treating disk cells with recombinant growth factor. Li, X., Leo, B.M., Beck, G., Balian, G., Anderson, G.D. Spine. (2004) [Pubmed]
  17. Correlation of GDF5 and connexin 43 mRNA expression during embryonic development. Coleman, C.M., Loredo, G.A., Lo, C.W., Tuan, R.S. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2003) [Pubmed]
  18. Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic. Shimaoka, H., Dohi, Y., Ohgushi, H., Ikeuchi, M., Okamoto, M., Kudo, A., Kirita, T., Yonemasu, K. Journal of biomedical materials research. Part A. (2004) [Pubmed]
  19. Molecular cloning of chicken metallothionein. Deduction of the complete amino acid sequence and analysis of expression using cloned cDNA. Wei, D.Y., Andrews, G.K. Nucleic Acids Res. (1988) [Pubmed]
  20. Glyoxalase I in detoxification: studies using a glyoxalase I transfectant cell line. Ranganathan, S., Walsh, E.S., Tew, K.D. Biochem. J. (1995) [Pubmed]
  21. Structure of the gene encoding mouse adipose differentiation-related protein (ADRP). Eisinger, D.P., Serrero, G. Genomics (1993) [Pubmed]
  22. Expression of cytochrome P4501b1 (Cyp1b1) during early murine development. Stoilov, I., Rezaie, T., Jansson, I., Schenkman, J.B., Sarfarazi, M. Mol. Vis. (2004) [Pubmed]
  23. A single residue of GDF-5 defines binding specificity to BMP receptor IB. Nickel, J., Kotzsch, A., Sebald, W., Mueller, T.D. J. Mol. Biol. (2005) [Pubmed]
  24. Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution. Tucker, A.S., Watson, R.P., Lettice, L.A., Yamada, G., Hill, R.E. Development (2004) [Pubmed]
  25. Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad. Nakahara, T., Tominaga, K., Koseki, T., Yamamoto, M., Yamato, K., Fukuda, J., Nishihara, T. Cell. Signal. (2003) [Pubmed]
  26. Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family. Storm, E.E., Kingsley, D.M. Development (1996) [Pubmed]
  27. Developmental failure of phalanges in the absence of growth/differentiation factor 5. Takahara, M., Harada, M., Guan, D., Otsuji, M., Naruse, T., Takagi, M., Ogino, T. Bone (2004) [Pubmed]
  28. Alteration of a developmentally regulated, heat-stable polypeptide in the lens of the Philly mouse. Implications for cataract formation. Nakamura, M., Russell, P., Carper, D.A., Inana, G., Kinoshita, J.H. J. Biol. Chem. (1988) [Pubmed]
  29. Retroviral transduction and oncogenic selection of a cDNA encoding Dbs, a homolog of the Dbl guanine nucleotide exchange factor. Whitehead, I., Kirk, H., Kay, R. Oncogene (1995) [Pubmed]
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