Apoptotic cell death in the mouse limb and its suppression in the hammertoe mutant.

We examined the importance of cell death in producing the limb deformity phenotype of the Hammertoe mouse. In order to make this evaluation, we first combined several techniques to verify the reliability of cell death markers in the normal mouse limb. In the normal limb, cell death occurs between Days 10.5 and 15.5 in the anterior, interdigital, and posterior zones. Morphological examination and staining for acid phosphatase or macrophages all reveal regions of cell death by detecting phagocytosis, while in situ end labeling of DNA defines nuclear degeneration as apoptotic. The phagocytes display surface markers characteristic of macrophages. The Hammertoe mutant shows strongly reduced cell death only in the interdigital region. This result is consistent with the phenotype and suggests that the mutation influences the patterning or control of cell death rather than its mechanism.