Comprehensive Phenotypic Data Packages

Metabolic Disorders: CAT Scan

Osteoporosis is characterized by a decreased bone mineral density due to a deficiency in bone production or increased bone absorption resulting in brittle bones. Specialized microcomputed tomography (micro-CT) machines have been developed with the capacity to provide quantitative and imaging data on the three-dimensional structure of mouse bones. This technique has been used to demonstrate the efficacy of parathyroid hormone in a mouse model of osteoporosis (Alexander et al., 2001) and to describe in three dimensions the changes in bone resulting from the osteopetrotic mutation, which leads to osteopetrosis (Abe et al., 2000). We use a Scanco Medical µCT40 machine for measurements of bone mass. This machine permits visualization of both trabecular and cortical bone structure, which is critical in evaluating overall bone quality. This is a much more sensitive analysis of bone than can be achieved using DEXA alone and is a specialized test for osteoporosis that we have implemented as part of our phenotypic analysis.

The assay is performed on dissected bone specimens. This permits visualization of trabecular bone structure, which is critical in evaluating overall bone quality. The µCT40 scans dissected bones and provides detailed information on bone mass and architecture. Multiple bones are placed into sample holders and scanned automatically. The researcher than uses instrument software to select bone regions of interest for analysis. Trabecular bone parameters are analyzed in the fifth lumbar vertebrae (LV5) at 16 micrometer resolution and cortical bone parameters are analyzed in the femur midshaft at a resolution of 20 micrometers.

Displayed below is a sample graph of how trabecular bone parameters are presented. In comprehensive phenotypic data packages graphs are interactive. Raw or calculated data and statistics can be seen by clicking on points in the graph. cat scan
Figure illustrates trabecular bone volume (left), trabecular number (center), and trabecular thickness (right) of mutant mice. Trabecular parameters of wild type littermates (green circle), homozygous (red diamond), and recent historical wild type (purple line) mice are plotted against long-term historical values (± 2 standard deviations) for wild type animals (green shading). Recent wild type values are calculated from data collected within 60 days of current measures and long-term historical values are derived from data collected on more than 10,000 wild type mice.


References

Abe S, Watanabe H, Hirayama A, Shibuya E, Hashimoto M, Ide Y. (2000) Morphological study of the femur in osteopetrotic (op/op) mice using microcomputed tomography, Br J Radiol, 73:1078-1082.

Alexander JM, Bab I, Fish S, Muller R, Uchiyama T, Gronowicz G, Nahounou M, et al. (2001) Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice, J Bone Miner Res, 16:1665-1673.