Screening Gene Knockout Mice for Variation in Bone Mass: Analysis by μCT and Histomorphometry
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.
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.
KeywordsIMPC and KOMP Bone phenotyping μCT Histomorphometry Web portal
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.
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