Cortisone-induced cleft palate in A/J mice: Failure of palatal shelf contact

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Abstract
Although cortisone treatment for induction of cleft palate in mice has been shown to delay the time of palatal shelf elevation, the effects of delayed elevation of shelf contact have not been critically evaluated in a cortisone-sensitive mouse strain. The objective of this study was to evaluate palatal development in cortisone-treated A/J mice in order to determine whether the shelves make contact upon elevation. Morphometric analysis of frozen sections revealed that cortisone-treated shelves were smaller than control shelves with apparent reductions in both the content of extracellular matrix and the number of cells. At a light microscopic level, thinning of medial epithelium in cortisone-treated palates appeared similar to that in untreated palates with spontaneous cleft lip and palate. Shelf elevation was delayed by approximately 12 hours and only half of the cortisone-treated palates achieved complete horizontal positioning of the shelves in all regions of the palate. Immediately after elevation, all control palates had extensive vertical contact along the complete length of the palate. In contrast, approximately 20% of the cortisone-treated fetuses had contact between the shelves in the middle palate region only, with the mean area of contact only 20% as large as in control fetuses. As a result, the net shelf contact in all the cortisone-treated fetuses was only 4% of the potential contact shown in control fetuses. Therefore, failure of the palatal shelves to elevate and make extensive contact appeared to be the major factor contributing to cortisone-induced cleft palate in A/J mice.