ABSTRACT
Historically, the foundation for assessing lethal phenotypes in developing mice has been assessment for structural defects and, to a lesser degree, functional deciencies. Routine techniques for characterizing anatomic abnormalities include qualitative macroscopic and light microscopic examinations, supplemented as needed by electron microscopy (Chapter 13) and quantitative methods to measure the dimensions,7,13 volume,89 or cell numbers12 in particular structures (Chapter 12). The primary difculties with such classic approaches to structural analysis are that a thorough assessment of any given organ is (1) quite laborious due to the requirement for extensive interval (step) or consecutive (serial) sectioning, which in turn (2) necessitates destruction of the physical specimen to produce a series of two-dimensional (2D) levels showing the structure in a specic planar orientation. Therefore, a complete appreciation of anatomic lesions traditionally has entailed the tedious fabrication of a three-dimensional (3D) construct by mental or physical realignment (stacking) and merging of multiple 2D images.
