Alternative titles; symbols
HGNC Approved Gene Symbol: BMP8B
Cytogenetic location: 1p34.2 Genomic coordinates (GRCh38): 1:39,757,182-39,788,865 (from NCBI)
The bone morphogenetic proteins (BMPs) are a family of secreted signaling molecules that can induce ectopic bone growth. Many BMPs, including BMP8B, are part of the transforming growth factor-beta (TGFB) superfamily (see 190180) (Ozkaynak et al., 1992).
Using a mouse Op2 probe, Ozkaynak et al. (1992) isolated a novel BMP cDNA, which they designated OP2, from a human hippocampus library. The predicted 402-amino acid OP2 protein is processed into a 139-amino acid mature form. In the TGFB domain, OP2 shows 74% amino acid sequence identity to OP1 (BMP7; 112267), and 55 to 74% identity to other BMPs. In mice, Northern blot analysis revealed high levels of Op2 mRNA as 3- and 5-kb transcripts in early embryos, but no detectable levels in any organs studied.
Using quantitative RT-PCR, Whittle et al. (2012) detected variable Bmp8b expression in all mouse tissues examined, with high expression in testis and brown adipose tissue, much lower expression in brain and subcutaneous white adipose tissue, and very low expression in gonadal white adipose tissue, liver, kidney, heart, and skeletal muscle.
By interspecific backcross analysis, DiLeone et al. (1997) mapped the mouse Bmp8 gene to chromosome 4. Based on homology of synteny, they mapped the human gene to 1p35-p32.
Hartz (2012) mapped the BMP8B gene to chromosome 1p34.2 based on an alignment of the BMP8B sequence (GenBank BC023526) with the genomic sequence (GRCh37).
Whittle et al. (2012) found that expression of Bmp8b in mice was upregulated by refeeding after fasting and by activation of thermogenic responses. Reporter gene assays revealed that the Bmp8b promoter could be induced by thermogenic thyroid hormone receptor beta-1 (THRB; 190160) and by PPAR-alpha (PPARA; 170998) or PPAR-gamma (PPARG; 601487). Treatment of mouse brown adipocytes with recombinant human BMP8B increased Smad (see 601595) phosphorylation and activation of hormone-sensitive lipase (LIPE; 151750) and AMPK (see 602739). BMP8B increased the lipolytic response to norepinephrine, and inhibition of Alk7 (ACVR1C; 608981) antagonized this effect.
Whittle et al. (2012) reported that Bmp8b -/- mice were viable and healthy but infertile due to defective primordial germ cell formation. A significant number of Bmp8b -/- pups suffered early death, but survival increased in a warm environment. Bmp8b -/- mice were prone to weight gain, particularly on a high fat diet, and they showed reduced core body temperature and impaired adrenergic-dependent thermogenic capacity. Intracerebroventricular treatment of Bmp8b -/- mice with recombinant human BMP8B resulted in marked weight loss and increased core body temperature. The central thermogenic action of BMP8B was dependent upon activation levels of hypothalamic Ampk. Whittle et al. (2012) concluded that BMP8B has a fundamental role in energy balance regulation in both the hypothalamus and brown adipose tissue.
DiLeone, R. J., King, J. A., Storm, E. E., Copeland, N. G., Jenkins, N. A., Kingsley, D. M. The Bmp8 gene is expressed in developing skeletal tissue and maps near the achondroplasia locus on mouse chromosome 4. Genomics 40: 196-198, 1997. [PubMed: 9070944] [Full Text: https://doi.org/10.1006/geno.1996.4533]
Hartz, P. A. Personal Communication. Baltimore, Md. 10/19/2012.
Ozkaynak, E., Schnegelsberg, P. N. J., Jin, D. F., Clifford, G. M., Warren, F. D., Drier, E. A., Oppermann, H. Osteogenic protein-2: a new member of the transforming growth factor-beta superfamily expressed in early embryogenesis. J. Biol. Chem. 267: 25220-25227, 1992. [PubMed: 1460021]
Whittle, A. J., Carobbio, S., Martins, L., Slawik, M., Hondares, E., Vazquez, M. J., Morgan, D., Csikasz, R. I., Gallego, R., Rodriguez-Cuenca, S., Dale, M., Virtue, S., Villarroya, F., Cannon, B., Rahmouni, K., Lopez, M., Vidal-Puig, A. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 149: 871-885, 2012. [PubMed: 22579288] [Full Text: https://doi.org/10.1016/j.cell.2012.02.066]