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

Curr Osteoporos Rep. 2018 Apr;16(2):77-94. doi: 10.1007/s11914-018-0421-4.

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. 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: Bone phenotyping; Histomorphometry; IMPC and KOMP; Web portal; μCT.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bone and Bones / diagnostic imaging*
  • Bone and Bones / pathology
  • Databases, Factual
  • Femur / diagnostic imaging*
  • Femur / pathology
  • Genotype
  • Information Management
  • Mice
  • Mice, Knockout
  • Phenotype
  • Program Development
  • Severity of Illness Index
  • Sex Characteristics
  • Spine / diagnostic imaging*
  • Spine / pathology
  • X-Ray Microtomography