Conditional expression of human bone Gla protein in osteoblasts causes skeletal abnormality in mice

Bone Gla protein (BGP), also known as osteocalcin, is one of the most abundant γ-carboxylated noncollagenous protein in bone matrix and plays important roles in mineralization and calcium ion homeostasis. BGP is synthesized specifically in osteoblasts; however, its precise function in bone metabolism has not been fully elucidated. To investigate the in vivo function of human BGP (hBGP), we generated CAG-GFPfloxed-hBGP transgenic mice carrying a transgene cassette composed of the promoter and a floxed GFP linked to hBGP cDNA. The mice were crossed with ColI-Cre mice, which express the Cre recombinase driven by the mouse collagen type 1a1 gene promoter, to obtain hBGPColI conditional transgenic mice that expressed human BGP in osteoblasts. The hBGPColI mice did not survive more than 2 days after birth. The analysis of the 18.5-day post coitum fetuses of the hBGPColI mice revealed that they displayed abnormal skeletal growth such as deformity of the rib and short femur and cranium lengths. Moreover, increased BGP levels were detected in the serum of the neonates. These findings indicate that hBGP expression in osteoblasts resulted in the abnormal skeletal growth in the mice. Our study provides a valuable model for understanding the fundamental role of BGP in vivo.

► Conditional transgenic mice expressing human BGP in osteoblasts were generated.
► The mice die within 2 days after birth and show abnormal skeletal growth.
► This model is useful for the understanding of the fundamental role of BGP in vivo.