Sh3Pxd2bnee-/-マウス：Frank-ter-Haar症候群における新たな発生学的特徴を明らかにする魅力的なモデル

Frank-ter-Haar syndrome (FTHS) is an inherited disease caused by mutations in the SH3PXD2B gene, encoding for the podosomal adaptor protein TKS4. FTHS is characterized by multiple skeletal abnormalities, developmental delay and severe craniofacial dysmorphology. This study characterized in-depth the calvarial phenotype of a mouse model of FTHS and investigates the potential underlying molecular and transcriptomic mechanisms. The Sh3Pxd2bnee-/- mouse presents with craniofacial malformations, disrupted suture patterning, decreased osteoregeneration, cell proliferation and migration both in vitro and in vivo and impaired podosome formation. Transcriptomic analysis revealed downregulation of genes involved in ribosome biogenesis. Moreover, ribosomal RNA accumulates in cell protrusions of migrating cells. We established that the craniofacial phenotype of the Sh3Pxd2bnee-/- mouse is governed by impaired cell migration and proliferation due to dysfunctional podosome formation, particularly in neural-crest derived tissues. Transcriptomic and molecular data suggest altered ribosome-related processes, though further investigation is needed to clarify the underlying mechanisms.