Defective Incisor Development in Smad Interacting Protein 1 (Sip1) Null Mice

Objectives

The aim of this study is to histologically and morphologically describe the dental and craniofacial manifestations of a novel mouse model involving a conditional mutation in the Smad Interacting Protein 1 (Sip1) gene.

Materials and Methods

Since targeted inactivation of Sip1 results in early embryonic lethality, tissue-specific inactivation of Sip1 was carried out by using Prx1-Cre mice. Embryos at 14.5 days post coitum (dpc), 15.5 dpc, 16.5 dpc and 18.5 dpc were analysed, as well as newborn and five-month-old Sip1 null mice, by means of immunohistochemistry (primary antibody: β-catenin and Ki67) and microscopic morphological examination, and the results were compared with those of wild-type mice. The Mann–Whitney U test was used to compare the dentofacial measurements between the knockout and wild-type mice.

Results

Differences in incisor position and shape were detected at 15.5 dpc. Mutant newborns presented with broadened calvarial sutures, hypoplastic mandibles, serrated alveolar processes, shorter lower incisors, and 10% of them had an extra cusp. Five-month-old mutants presented total suture disappearance, a hypoplastic maxilla and long, curved lower incisors.

Conclusions

These observations suggest that Sip1 is involved in dental and craniofacial development, leading to several dental and skull malformations.

Clinical Relevance

This study of conditional Sip1 mutations in this mouse model provides crucial insights into potential mechanisms underlying human craniofacial and dental anomalies, aiding diagnosis and therapeutic strategies.