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.