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

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We generated two novel <jats:italic>Sned1</jats:italic> knockout mouse strains and showed that <jats:italic>Sned1</jats:italic> 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 <jats:italic>Sned1</jats:italic> knockout resulted in growth defects, nasal cavity occlusion, and craniofacial malformations. <jats:italic>Sned1</jats:italic> is widely expressed in embryos, notably in neural-crest derivatives. We further show here that mice with a neural-crest-cell-specific deletion of <jats:italic>Sned1</jats:italic> survive, but display facial anomalies partly phenocopying the global knockout mice.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our results demonstrate requisite roles for SNED1 during development and neonatal survival. Importantly, the deletion of 2q37.3 in humans, a region that includes the <jats:italic>SNED1</jats:italic> locus, has been associated with facial dysmorphism and short stature.</jats:p></jats:sec>

Canine Bone Marrow-derived Mesenchymal Stem Cells: Genomics, Proteomics and Functional Analyses of Paracrine Factors

“…SNED1 is another factor found in canine MSC CM. Recently, it has been demonstrated that SNED1 is a crucial factor during development and neonatal survival (20). We demonstrate that some of the factors released by BMMSC CM are associated with angiogenic activity in the CAM assay.…”

“…The sushi, nidogen, and EGF-like domains (SNED1) protein is also known as an extracellular matrixcomponent. SNED1 knockout mouse strains have revealed that SNED1 is required during neonatal survival and development, especially in the development of the skeleton and neural crest-derived craniofacial structures (20). The last Cluster 4 (Supplemental Data 8) contained osteogenic factors involved in differentiation of MSCs, such as the osteoblast-specific factor and osteonectin-2 (21).…”

Genetic analysis of body weight in wild populations of medaka fish from different latitudes

“…Patients with a deletion in that region, with breakpoints at or within cytogenetic band 2q37, have a short stature among other features [51]. Sned1 might be involved in mouse skeletal development, as Sned1 knockout mice have craniofacial malformations and growth defects [52]. Therefore, we speculate that a functional difference in SNED1 protein activity caused by the amino substitution that distinguished Maizuru from Ginoza induced the difference in body weight.…”

A pan-cancer analysis of matrisome proteins reveals CTHRC1and LOXL2 as major ECM regulators across cancers

“…SNED1(Sushi, nidogen and EGF like domain containing protein-1) is a glycoprotein known to be involved in embryonic development [22]. Our pan-cancer analysis of matrisome genes differentially expressed and affecting survival in TCGA cancer types, identified SNED1 to be significantly downregulated in bladder, breast, colon, brain, kidney, lung, ovarian, adrenal, prostate, rectal, skin, testicular and uterine cancers while it was upregulated in only thymus cancer ( Figure 2A, C ).…”

“…SNED1 was recently discovered as a ECM glycoprotein whose exact function remains unknown [22,27]. SNED1 knockout mice die perinatally showing significant growth defects [22].…”