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Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

Nipbl Haploinsufficiency Leads to Delayed Outflow Tract Septation and Aortic Valve Thickening

Résumé

Cornelia de Lange Syndrome (CdLS) patients, who frequently carry a mutation in NIPBL, present an increased incidence of outflow tract (OFT)-related congenital heart defects (CHDs). Nipbl+/- mice recapitulate a number of phenotypic traits of CdLS patients, including a small body size and cardiac defects, but no study has specifically focused on the valves. Here, we show that adult Nipbl+/- mice present aortic valve thickening, a condition that has been associated with stenosis. During development, we observed that OFT septation and neural crest cell condensation was delayed in Nipbl+/- embryos. However, we did not observe defects in the deployment of the main lineages contributing to the semilunar valves. Indeed, endocardial endothelial-to-mesenchymal transition (EndMT), analysed via outflow tract explants, and neural crest migration, analysed via genetic lineage tracing, did not significantly differ in Nipbl+/- mice and their wild-type littermates. Our study provides the first direct evidence for valve formation defects in Nipbl+/- mice and points to specific developmental defects as an origin for valve disease in patients.
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hal-04598309 , version 1 (03-06-2024)

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Fanny Boulet, Gaelle Odelin, Alenca Harrington, Thomas Moore-Morris. Nipbl Haploinsufficiency Leads to Delayed Outflow Tract Septation and Aortic Valve Thickening. International Journal of Molecular Sciences, 2023, 24 (21), pp.15564. ⟨10.3390/ijms242115564⟩. ⟨hal-04598309⟩
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