Current Osteoporosis Reports

, Volume 16, Issue 2, pp 77–94 | Cite as

Screening Gene Knockout Mice for Variation in Bone Mass: Analysis by μCT and Histomorphometry

  • David W. Rowe
  • Douglas J. Adams
  • Seung-Hyun Hong
  • Caibin Zhang
  • Dong-Guk Shin
  • C. Renata Rydzik
  • Li Chen
  • Zhihua Wu
  • Gaven Garland
  • Dana A. Godfrey
  • John P. Sundberg
  • Cheryl Ackert-Bicknell
Genetics (M Johnson and S Ralston, Section Editors)
  • 78 Downloads
Part of the following topical collections:
  1. Topical Collection on Genetics

Abstract

Purpose of review

The international mouse phenotyping consortium (IMPC) is producing defined gene knockout mouse lines. Here, a phenotyping program is presented that is based on micro-computed tomography (μCT) assessment of distal femur and vertebra. Lines with significant variation undergo a computer-based bone histomorphometric analysis.

Recent findings

Of the 220 lines examined to date, approximately 15% have a significant variation (high or low) by μCT, most of which are not identified by the IMPC screen. Significant dimorphism between the sexes and bone compartments adds to the complexity of the skeletal findings. The μCT information that is posted at www.bonebase.org can group KOMP lines with similar morphological features. The histological data is presented in a graphic form that associates the cellular features with a specific anatomic group.

Summary

The web portal presents a bone-centric view appropriate for the skeletal biologist/clinician to organize and understand the large number of genes that can influence skeletal health. Cataloging the relative severity of each variant is the first step towards compiling the dataset necessary to appreciate the full polygenic basis of degenerative bone disease.

Keywords

IMPC and KOMP Bone phenotyping μCT Histomorphometry Web portal 

Notes

Compliance with Ethical Standards

Conflict of Interest

David Rowe, Seung-Hyun Hong, Caibin Zhang, Dong-Guk Shin, Renata Rydzik, Li Chen, Zhihua Wu, Gaven Garland, Dana Godfrey, and John Sundberg declare no conflict of interest. Cheryl Ackert-Bicknell reports grants from National Institutes of Health/NIAMS during the conduct of the study. Douglas Adams reports grants from National Institutes of Health.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

11914_2018_421_MOESM1_ESM.jpg (45 kb)
Fig. S1 Criteria for flagging a value as low or high in the search page (JPEG 45 kb)
11914_2018_421_MOESM2_ESM.jpg (119 kb)
Fig. S2 Screened KOMP lines fulfilling the category of normal bone mass (NBM) as identified as having a normal BV/TV and in the other measurements (NTV = normal total volume of the diaphyseal ROI, NTA = normal subperiosteal area, Tt.Ar, NWt = normal weight) (JPEG 118 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • David W. Rowe
    • 1
  • Douglas J. Adams
    • 2
  • Seung-Hyun Hong
    • 3
  • Caibin Zhang
    • 1
  • Dong-Guk Shin
    • 3
  • C. Renata Rydzik
    • 2
  • Li Chen
    • 1
  • Zhihua Wu
    • 1
  • Gaven Garland
    • 4
  • Dana A. Godfrey
    • 5
  • John P. Sundberg
    • 4
  • Cheryl Ackert-Bicknell
    • 5
  1. 1.Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, Biomaterials and Skeletal Development, School of Dental MedicineUniversity of Connecticut HealthFarmingtonUSA
  2. 2.Department of Orthopaedic Surgery, School of MedicineUniversity of Connecticut HealthFarmingtonUSA
  3. 3.Computer Science and Engineering, School of EngineeringUniversity of ConnecticutStorrsUSA
  4. 4.The Jackson LaboratoryBar HarborUSA
  5. 5.Center for Musculoskeletal Research, Department of Orthopaedics and RehabilitationUniversity of Rochester School of MedicineRochesterUSA

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