33 - Modeling Cerebro-costo-mandibular Syndrome (CCMS) with Tamoxifen-Induced Snrpb Deletion

Poster Board Number: 33
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Abstract Body : Heterozygous mutations in SNRPB, an essential core component of the five small ribonucleoprotein particles of the spliceosome, are responsible for Cerebro-costo-mandibular Syndrome (CCMS). CCMS is a rare congenital disorder commonly characterized by micrognathia (abnormally small jaw), cleft palate, and various degrees of rib abnormalities. Previously, we found that Snrpb heterozygous mouse embryos arrest shortly after implantation. Although heterozygous deletion of Snrpb in the developing brain and neural crest cells modeled craniofacial malformations found in CCMS patients, a model that can capture the full spectrum of CCMS symptoms is still lacking. Utilizing the tamoxifen (TAM) inducible Cre recombinase system, we generated heterozygous Snrpb deletion mid-gestation via tamoxifen injection. Here we characterized the phenotypes of mutant embryos with tamoxifen-induced Snrpb deletion from different developmental stages. Notably, in E17.5 mutant embryos, we identified CCMS-like rib abnormalities in addition to craniofacial malformations. Tamoxifen-induced deletion of Snrpb throughout the embryonic body, in all cell types, generates a better model of CCMS. By characterizing the etiology of observed abnormalities in this model, we look to identify disrupted transcripts and pathways with, potentially, greater clinical implications.