Knockout of the gene encoding the extracellular matrix protein SNED1 results in early neonatal lethality and craniofacial malformations
© 2020 American Association of Anatomists..
BACKGROUND: 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 breast cancer patient survival. Here, we sought to identify the roles of SNED1 during murine development.
RESULTS: We generated two novel Sned1 knockout mouse strains and showed that Sned1 is essential since homozygous ablation of the gene led to early neonatal lethality. Phenotypic analysis of the surviving knockout mice 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 by cell populations undergoing epithelial-to-mesenchymal transition, such as the neural crest cells. We further show that mice with a neural-crest-cell-specific deletion of Sned1 survive, but display facial anomalies partly phenocopying the global knockout mice.
CONCLUSIONS: 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 SNED1 locus, has been associated with facial dysmorphism and short stature.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:250 |
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| Enthalten in: |
Developmental dynamics : an official publication of the American Association of Anatomists - 250(2021), 2 vom: 15. Feb., Seite 274-294 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Barqué, Anna [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2022 Date Revised 02.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/dvdy.258 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315823437 |
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| 100 | 1 | |a Barqué, Anna |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Knockout of the gene encoding the extracellular matrix protein SNED1 results in early neonatal lethality and craniofacial malformations |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 18.01.2022 | ||
| 500 | |a Date Revised 02.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 American Association of Anatomists. | ||
| 520 | |a BACKGROUND: 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 breast cancer patient survival. Here, we sought to identify the roles of SNED1 during murine development | ||
| 520 | |a RESULTS: We generated two novel Sned1 knockout mouse strains and showed that Sned1 is essential since homozygous ablation of the gene led to early neonatal lethality. Phenotypic analysis of the surviving knockout mice 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 by cell populations undergoing epithelial-to-mesenchymal transition, such as the neural crest cells. We further show that mice with a neural-crest-cell-specific deletion of Sned1 survive, but display facial anomalies partly phenocopying the global knockout mice | ||
| 520 | |a CONCLUSIONS: 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 SNED1 locus, has been associated with facial dysmorphism and short stature | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a craniofacial features | |
| 650 | 4 | |a geometric morphometrics | |
| 650 | 4 | |a knockout mouse | |
| 650 | 4 | |a mandible | |
| 650 | 4 | |a neural crest cells | |
| 650 | 7 | |a Extracellular Matrix Proteins |2 NLM | |
| 650 | 7 | |a Snep protein, mouse |2 NLM | |
| 700 | 1 | |a Jan, Kyleen |e verfasserin |4 aut | |
| 700 | 1 | |a De La Fuente, Emanuel |e verfasserin |4 aut | |
| 700 | 1 | |a Nicholas, Christina L |e verfasserin |4 aut | |
| 700 | 1 | |a Hynes, Richard O |e verfasserin |4 aut | |
| 700 | 1 | |a Naba, Alexandra |e verfasserin |4 aut | |
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