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

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.