An osteocalcin-deficient mouse strain without endocrine abnormalities
Autoři:
Cassandra R. Diegel aff001; Steven Hann aff002; Ugur M. Ayturk aff002; Jennifer C. W. Hu aff002; Kyung-eun Lim aff004; Casey J. Droscha aff001; Zachary B. Madaj aff005; Gabrielle E. Foxa aff001; Isaac Izaguirre aff001; VAI Vivarium and Transgenics Core aff006; Noorulain Paracha aff007; Bohdan Pidhaynyy aff007; Terry L. Dowd aff008; Alexander G. Robling aff004; Matthew L. Warman aff002; Bart O. Williams aff001
Působiště autorů:
Program in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America
aff001; Orthopedic Research Labs, Boston Children’s Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
aff002; Musculoskeletal Integrity Program, Hospital for Special Surgery Research Institute, New York, New York, United States of America
aff003; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
aff004; Bioinformatics and Biostatistics Core, Van Andel Institute, Grand Rapids, Michigan, United States of America
aff005; Vivarium and Transgenics Core, Van Andel Institute, Grand Rapids, Michigan, United States of America
aff006; Department of Biology, Brooklyn College, Brooklyn, New York, United States of America
aff007; Department of Chemistry, Brooklyn College, Brooklyn, New York, United States of America
aff008; Ph.D. Program in Chemistry and Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York, United States of America
aff009
Vyšlo v časopise:
An osteocalcin-deficient mouse strain without endocrine abnormalities. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008361
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008361
Souhrn
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 mouse allele (Osc–) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 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-length Bglap or Bglap2 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-deficient mice with the Bglap/2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution.
Klíčová slova:
Blood – Blood sugar – Bone imaging – Messenger RNA – Mouse models – Osteocalcin – RNA sequencing – Testosterone
Zdroje
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