Discussion.

ABSTRACT

Each of the radiographic, histologic, whole mount, and three-dimensional computerized reconstruction techniques throws specific light on the vertebral, intervertebral disc, and rib abnormalities in the development of the pudgy mouse. The end result demonstrates a failure of both normal formation and normal segmentation in the pudgy mouse recognized now as a recessive genetic disorder in which mutations in the Delta-like 3 gene (Dll3) have been defined [2]. The variable appearance of the vertebral and rib abnormalities from mouse to mouse, including in particular the variable appearance in affected littermates, indicates that the gene abnormality alone does not account solely for the deformities seen. Once the gene abnormality is expressed early in embryogenesis, secondary effects, presumably by mechanisms of epigenetics, appear to play a significant role in outlining the abnormal pattern. The pudgy mouse and other genetically triggered axial developmental abnormalities represent excellent models to help unravel pathogenetic mechanisms whereby gene abnormalities are translated into three-dimensional structural abnormalities.