An osteocalcin-deficient mouse strain without endocrine abnormalities.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, c2005-
    • Subject Terms:
    • Abstract:
      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.
      Competing Interests: BOW is the recipient of a sponsored research agreement from Janssen Pharmaceuticals for work not directly related to these studies. BOW also is a member of the Scientific Advisory Board for Surrozen.
    • Comments:
      Comment in: PLoS Genet. 2020 Jun 2;16(6):e1008714. (PMID: 32484816)
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    • Grant Information:
      I01 BX001478 United States BX BLRD VA; IK6 BX003783 United States BX BLRD VA; United States HHMI Howard Hughes Medical Institute
    • Accession Number:
      104982-03-8 (Osteocalcin)
    • Publication Date:
      Date Created: 20200529 Date Completed: 20200730 Latest Revision: 20220816
    • Publication Date:
      20240105
    • Accession Number:
      PMC7255615
    • Accession Number:
      10.1371/journal.pgen.1008361
    • Accession Number:
      32463812