An osteocalcin-deficient mouse strain without endocrine abnormalities

by Cassandra R. Diegel, Steven Hann, Ugur M. Ayturk, Jennifer C. W. Hu, Kyung-eun Lim, Casey J. Droscha, Zachary B. Madaj, Gabrielle E. Foxa, Isaac Izaguirre, VAI Vivarium and Transgenics Core, Noorulain Paracha, Bohdan Pidhaynyy, Terry L. Dowd, Alexander G. Robling, Matthew L. Warman, Bart O. Williams Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient m ouse allele (Osc–) in which the 2 OCN-encoding genes in mice,Bglap andBglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a newBglap andBglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-lengthBglap orBglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, μCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc−allele, serum glucose levels and male fertility in the OCN-deficien...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research