The roles of Tbx22 in craniofacial and palate development

Objectives: Mutations in the TBX22 gene have been associated with X-linked cleft palate and ankyloglossia in humans and TBX22 mRNA expression patterns in human and mouse embryos correlated with the developmental defects. The objectives of this project are to generate a Tbx22 mutant mouse model and to understand the molecular mechanims involving Tbx22 in palatal and craniofacial development. Methods: We generated mice deficient in the Tbx22 gene though homologous recombination in embryonic stem cells. We initially generated mice with deletion of the first three coding exons of the Tbx22 gene and found that neither hemizygous mutant males nor homozygous females had cleft palate defects. We re-targeted the Tbx22 gene and generated mice carrying a complete null mutation replacing the Tbx22 coding region with the bacterial lacZ gene. Results: In a mixed 129/C57 genetic background, less than 10% of the Tbx22 null mutant mice exhibited cleft palate, and approximately 15% of Tbx22 null mutant mice exhibited ankyloglossia and postnatal growth retardation. Conclusions: These data indicate, whereas Tbx22 is a true ortholog of the human TBX22 gene and they exhibited similar expression patterns during palate development in mice and humans, that Tbx22 plays a minor role in palate development in mice. This work was supported by NIH/NIDCR grants R01 DE013681.