# The Sh3Pxd2bnee−/− mouse reveals developmental features of Frank-ter Haar syndrome

## TL;DR

A mouse model of Frank-ter Haar syndrome shows craniofacial issues due to impaired cell migration and ribosome-related problems.

## Contribution

The study reveals that Sh3Pxd2bnee−/− mice exhibit craniofacial malformations linked to dysfunctional podosomes and altered ribosome processes.

## Key findings

- Sh3Pxd2bnee−/− mice show craniofacial malformations and disrupted suture patterning.
- Reduced osteoregeneration and impaired cell proliferation and migration are observed in these mice.
- Transcriptomic analysis shows downregulation of genes involved in ribosome biogenesis.

## Abstract

Frank-ter Haar syndrome (FTHS) is an inherited disease associated with variants of the SH3PXD2B gene, encoding for the podosomal adaptor protein known as TKS4. FTHS is characterized by multiple skeletal abnormalities, developmental delay and severe craniofacial dysmorphology. This study provides an in-depth characterization of 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 and disrupted suture patterning, as well as reduced osteoregeneration and decreased cell proliferation and migration observed 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, although further investigation is needed to clarify the underlying mechanisms.

Summary: The Sh3Pxd2bnee−/− mouse, a model for FTHS, reveals impaired proliferation, podosome formation, migration, specifically in neural crest tissues, and potentially altered ribosome-related processes leading to craniofacial malformations.