The GWAS candidate far upstream element binding protein 3 (FUBP3) is required for normal skeletal growth, and adult bone mass and strength in mice

Bone mineral density (BMD) and height are highly heritable traits for which hundreds of genetic loci have been linked through genome wide association studies (GWAS). FUBP3 is a DNA and RNA binding protein best characterised as a transcriptional regulator of c-Myc, but little is known about its role in vivo. Single nucleotide polymorphisms in FUBP3 at the 9q34.11 locus have been associated with BMD, fracture and height in multiple GWAS, but FUBP3 has no previously established role in the skeleton. We analysed Fubp3-deficient mice to determine the consequence of FUBP3 deficiency in vivo. Mice lacking Fubp3 had reduced survival to adulthood and impaired skeletal growth. Bone mass was decreased, most strikingly in the vertebrae, with altered trabecular micro-architecture. Fubp3 deficient bones were also weak. These data provide the first functional demonstration that Fubp3 is required for normal skeletal growth and development and maintenance of adult bone structure and strength, indicating that FUBP3 contributes to the GWAS association of 9q34.11 with variation in height, BMD and fracture.