Evidence map›Paper›PMID 32463812›Full record

ArticlePLoS genetics2020

An osteocalcin-deficient mouse strain without endocrine abnormalities.

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 and 6 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
12.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
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  12. The role of bone in whole-body energy metabolism.Nature reviews. Endocrinology · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Bone and muscle crosstalk in ageing and disease.Nature reviews. Endocrinology · 2025
    Review
  17. Review
  18. Bone development by Hedgehog and Wnt signaling, Runx2, and Sp7.Journal of bone and mineral metabolism · 2025
    Review
  19. Review
  20. Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 1 country.

Cassandra R DiegelProgram in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America.
Steven HannOrthopedic Research Labs, Boston Children's Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
Ugur M AyturkOrthopedic Research Labs, Boston Children's Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
Jennifer C W HuOrthopedic Research Labs, Boston Children's Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0002-3712-5427
Kyung-Eun LimDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Casey J DroschaProgram in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America.
Zachary B MadajBioinformatics and Biostatistics Core, Van Andel Institute, Grand Rapids, Michigan, United States of America.ORCID 0000-0003-2330-0500
Gabrielle E FoxaProgram in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America.ORCID 0000-0001-7685-8079
Isaac IzaguirreProgram in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America.ORCID 0000-0002-9796-6850
Vai Vivarium And Transgenics CoreVivarium and Transgenics Core, Van Andel Institute, Grand Rapids, Michigan, United States of America.
Noorulain ParachaDepartment of Biology, Brooklyn College, Brooklyn, New York, United States of America.
Bohdan PidhaynyyDepartment of Biology, Brooklyn College, Brooklyn, New York, United States of America.ORCID 0000-0002-3982-2410
Terry L DowdDepartment of Chemistry, Brooklyn College, Brooklyn, New York, United States of America.ORCID 0000-0001-9023-0093
Alexander G RoblingDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.ORCID 0000-0002-3989-4780
Matthew L WarmanOrthopedic Research Labs, Boston Children's Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
Bart O WilliamsProgram in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America.ORCID 0000-0002-5261-5301
Van Andel Institute · USBoston Children's Hospital · USBrooklyn College · USIndiana University School of MedicineHospital for Special Surgery · USThe Graduate Center, CUNY · US

Funding

Lrp5 signaling in bone mechanotransduction and metabolismR01AR053237 · NIAMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI ALEXANDER G ROBLING, Matthew L Warman · 2005 to 2026
$9.4M
Translational Imaging and Phenotyping CoreP30AR075042 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI PAOLA DIVIETI PAJEVIC · 2019 to 2026
$7.4M
Non-heritable genetic diseases of the skeletal system: Pathogenesis and TreatmentR01AR064231 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI WARMAN, MATTHEW L · 2014 to 2018
$1.9M
Generation and Initial Characterization of Osteocalcin-Deficient RatsR21AR068668 · NIAMS · VAN ANDEL RESEARCH INSTITUTE · PI WILLIAMS, BART O · 2015 to 2016
$460k
Lrp5 and Lrp6 signaling in bone mechanotransduction and metabolismR56AR053237 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI ROBLING, ALEXANDER G, WARMAN, MATTHEW L · 2023 to 2023
$349k
BLRD Research Career Scientist Award ApplicationIK6BX003783 · VA · RLR VA MEDICAL CENTER · PI ALEXANDER G ROBLING · 2017 to 2026
–
BLRD VA I01 BX001478BLRD VA IK6 BX003783Howard Hughes Medical InstituteNIAMS NIH HHS P30 AR075042NIAMS NIH HHS R01 AR053237NIAMS NIH HHS R01 AR064231NIAMS NIH HHS R21 AR068668NIAMS NIH HHS R56 AR053237
6 · The paper itself

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.

Indexed as

AnimalsBone and BonesBone DensityEndocrine SystemFemaleFertilityInsulin ResistanceMaleMiceMice, Inbred C57BLMice, KnockoutOsteocalcinOsteocalcin

Identifiers

PMID32463812
PMCPMC7255615
OpenAlexW3028775863

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.