HGNC Approved Gene Symbol: BMP5
Cytogenetic location: 6p12.1 Genomic coordinates (GRCh38): 6:55,753,653-55,875,590 (from NCBI)
Bone morphogenetic proteins were originally identified by the ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site (Urist, 1965). Like other BMPs, BMP5 is a member of the transforming growth factor-beta (see TGFB1; 190180) superfamily of regulatory molecules. Based on amino acid sequence homology, BMP5, BMP6 (112266), and BMP7 (112267) constitute a subfamily of BMPs (summary by Hahn et al., 1992).
Using bovine Bmp6 to screen a U2-OS cell line cDNA library, Celeste et al. (1990) cloned full-length BMP5. The deduced 454-amino acid protein contains a hydrophobic leader sequence followed by a proprotein region and a C-terminal 138-amino acid mature domain with 3 potential N-glycosylation sites. Sequence comparison suggested that BMP2 (112261), BMP5, BMP6, and BMP7 form a BMP subfamily. Northern blot analysis detected a major BMP5 transcript of about 2.8 kb in the U2-OS cell line.
Using RT-PCR, Beck et al. (2001) found that Bmp5 was expressed in the developing rat superior cervical ganglion at embryonic day 20, corresponding to the initial extension of primary dendrites, and in the early postnatal period during maximal dendritic growth. Bmp5 was not detected in adult superior cervical ganglion cells. Immunofluorescence analysis of cultured superior cervical ganglion cells detected Bmp5 throughout the cell body of glial cells, with exclusion from the nucleus, and in soma and processes of neurons.
Beck et al. (2001) showed that recombinant human BMP5 and BMP7 independently elicited dendritic growth in cultured rat superior cervical neurons. Their effects were not additive. BMP5-induced dendritic growth was associated with Smad1 (601595) phosphorylation, but not altered Smad1 expression. BMP5-induced dendritic outgrowth was inhibited by the extracellular domain of BMP receptor IA (BMPR1A; 601299), noggin (NOG; 602991), and follistatin (FST; 136470).
Sakaue et al. (1996) determined that the promoter region of the BMP5 gene contains 2 transcriptional start sites, a canonical TATA box, and a number of consensus recognition sequences, including GATA1 (305371) and engrailed (EN1; 131290). Functional analysis suggested that the promoter region lacks a silencer element.
Using human-rodent somatic cell hybrid lines and cDNA probes, Hahn et al. (1992) mapped BMP5 and BMP6 to human chromosome 6, while BMP7 was found to be syntenic with BMP2 on human chromosome 20.
Kingsley et al. (1992) showed that mutations at the classic mouse locus short ear (se) on chromosome 9 disrupt the mouse Bmp5 gene. Complete deletion of Bmp5 coding sequences is compatible with viability. Mutations at the 'short ear' locus are associated with a specific spectrum of morphologic alterations in the ear and many internal skeletal structures, suggesting that bone morphogenetic proteins have been aptly named. The mutant animals also show a defect in repair of bone fractures and a number of soft tissue abnormalities including lung cysts, liver granulomas, and hydropic kidneys. Further study of these mice should be useful for determining how BMPs control the growth and patterning of skeletal tissue, and what roles these genes play in other organ systems as well.
The regulatory regions surrounding many genes may be large and difficult to study using standard transgenic approaches. DiLeone et al. (2000) described the use of bacterial artificial chromosome (BAC) clones to survey rapidly hundreds of kilobases of DNA for potential regulatory sequences surrounding the mouse Bmp5 gene. Simple coinjection of large insert clones with lacZ reporter constructs recapitulated all of the sites of expression observed previously with numerous small constructs covering a large, complex regulatory region. The coinjection approach made it possible to survey rapidly other regions of the Bmp5 gene for potential control elements, to confirm the location of several elements predicted from previous expression studies using regulatory mutations at the Bmp5 locus, to test whether Bmp5 control regions act similarly on endogenous and foreign promoters, and to show that Bmp5 control elements are capable of rescuing phenotypic effects of a Bmp5 deficiency. This rapid approach identified new Bmp5 control regions responsible for controlling the development of specific anatomic structures in the vertebrate skeleton. DiLeone et al. (2000) suggested that a similar approach may be useful for studying complex control regions surrounding many other genes important in embryonic development and human disease.
Beck, H. N., Drahushuk, K., Jacoby, D. B., Higgins, D., Lein, P. J. Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured sympathetic neurons. BMC Neurosci. 2: 12, 2001. Note: Electronic Article. [PubMed: 11580864] [Full Text: https://doi.org/10.1186/1471-2202-2-12]
Celeste, A. J., Iannazzi, J. A., Taylor, R. C., Hewick, R. M., Rosen, V., Wang, E. A., Wozney, J. M. Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. Proc. Nat. Acad. Sci. 87: 9843-9847, 1990. [PubMed: 2263636] [Full Text: https://doi.org/10.1073/pnas.87.24.9843]
DiLeone, R. J., Marcus, G. A., Johnson, M. D., Kingsley, D. M. Efficient studies of long-distance Bmp5 gene regulation using bacterial artificial chromosomes. Proc. Nat. Acad. Sci. 97: 1612-1617, 2000. [PubMed: 10677507] [Full Text: https://doi.org/10.1073/pnas.97.4.1612]
Hahn, G. V., Cohen, R. B., Wozney, J. M., Levitz, C. L., Shore, E. M., Zasloff, M. A., Kaplan, F. S. A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7. Genomics 14: 759-762, 1992. [PubMed: 1427904] [Full Text: https://doi.org/10.1016/s0888-7543(05)80181-8]
Kingsley, D. M., Bland, A. E., Grubber, J. M., Marker, P. C., Russell, L. B., Copeland, N. G., Jenkins, N. A. The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF-beta superfamily. Cell 71: 399-410, 1992. [PubMed: 1339316] [Full Text: https://doi.org/10.1016/0092-8674(92)90510-j]
Sakaue, M., Kitazawa, S., Nishida, K., Kitazawa, R., Maeda, S. Molecular cloning and characterization of human bone morphogenic protein (BMP)-5 gene promoter. Biochem. Biophys. Res. Commun. 221: 768-772, 1996. [PubMed: 8630036] [Full Text: https://doi.org/10.1006/bbrc.1996.0671]
Urist, M. R. Bone: formation by autoinduction. Science 150: 893-899, 1965. [PubMed: 5319761] [Full Text: https://doi.org/10.1126/science.150.3698.893]