Knockout of the gene encoding the extracellular matrix protein SNED1 results in early neonatal lethality and craniofacial malformations

BackgroundThe extracellular matrix (ECM) is a fundamental component of multicellular organisms that orchestrates developmental processes and controls cell and tissue organization. We previously identified the novel ECM protein SNED1 as a promoter of breast cancer metastasis and showed that its level of expression negatively correlated with survival of breast cancer patients. Here we sought to identify the roles of SNED1 during murine development and in physiology. ResultsWe generated two novel Sned1 knockout mouse strains and showed that Sned1 is essential since homozygous ablation of the gene led to ~67% early neonatal lethality. Phenotypic analysis of the surviving knockout mice obtained revealed a role for SNED1 in the development of craniofacial and skeletal structures since Sned1 knockout resulted in growth defects, nasal cavity occlusion, and craniofacial malformations. Sned1 is widely expressed in embryos, notably in neural-crest derivatives. We further show here that mice with a neural-crest-cell-specific deletion of Sned1 survive, but display facial anomalies partly phenocopying the global knockout mice. ConclusionsOur results demonstrate requisite roles for SNED1 during development and neonatal survival. Importantly, the deletion of 2q37.3 in humans, a region that includes the SNED1 locus, has been associated with facial dysmorphism and short stature.