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An osteocalcin-deficient mouse strain without endocrine abnormalities.

Cassandra R Diegel1, Steven Hann2, Ugur M Ayturk2,3

  • 1Program in Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, Michigan, United States of America.

Plos Genetics
|May 29, 2020
PubMed
Summary
This summary is machine-generated.

New research introduces a double-knockout mouse model for osteocalcin (OCN) deficiency, revealing no significant impact on glucose metabolism or male fertility, contrary to previous findings. This OCN-deficient mouse strain is now available for further investigation.

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Area of Science:

  • Endocrinology
  • Bone Biology
  • Genetics

Background:

  • Osteocalcin (OCN) is a bone-derived hormone influencing glucose metabolism and male fertility.
  • Previous studies used an OCN-deficient mouse model (Osc-) with conflicting results.
  • A new OCN-deficient mouse model is needed for clearer understanding.

Purpose of the Study:

  • To generate and characterize a new OCN-deficient mouse model using CRISPR/Cas9.
  • To investigate the physiological effects of complete OCN deficiency.
  • To compare findings with the previously established OCN-deficient mouse model.

Main Methods:

  • CRISPR/Cas9 gene editing to create Bglap and Bglap2 double-knockout (dko) mice.
  • FTIR imaging to analyze cortical bone composition.
  • μCT and 3-point bending tests for bone mass and strength assessment.
  • Measurement of serum glucose levels and evaluation of male fertility.

Main Results:

  • Homozygous dko mice lack full-length Bglap/Bglap2 mRNA and detectable serum OCN.
  • Cortical bone showed altered collagen maturity and carbonate to phosphate ratio.
  • Bone mass and strength were comparable to wild-type littermates.
  • No significant differences in serum glucose levels or male fertility were observed compared to wild-type mice.

Conclusions:

  • The new Bglap/Bglap2 dko mouse model exhibits OCN deficiency without the previously reported endocrine effects on glucose metabolism and male fertility.
  • The discrepancy with the Osc- allele model suggests potential influences of genetic background, environment, or off-target gene effects.
  • This novel OCN-deficient mouse strain is provided to the research community for further validation and study.