Loss of function mutation of Eftud2, the gene responsible for mandibulofacial dysostosis with microcephaly (MFDM), leads to pre-implantation arrest in mouse

• DOI: 10.1371/journal.pone.0219280
• Publication Date: 2019-07-05T17:36:36Z
• Authors: Marie-Claude Beau...; Anissa Djedid; Kevin Daupin; Kayla Clokie; Shruti Kumar; Jacek Majewski; Loydie Anne Jerom...
• Keywords: Microcephaly; Gene targeting

Mutations in EFTUD2 are responsible for the autosomal dominant syndrome named MFDM (mandibulofacial dysostosis with microcephaly). However, it is not clear how reduced levels of cause abnormalities associated this syndrome. To determine if mouse can serve as a model uncovering etiology found patients, we used situ hybridization to characterize expression Eftud2 during development, and CRISPR/Cas9 generate mutant line deletion exon 2 gene. We that was expressed throughout embryonic though its enriched developing head craniofacial regions. Additionally, heterozygous embryos had mRNA protein levels. Moreover, were born at expected Mendelian frequency, viable fertile despite being developmentally delayed. In contrast, homozygous post-implantation but present frequency day (E) 3.5. Furthermore, only wild-type E3.5 survived ex vivo culture. Our data indicate precusor structures affected patients show mice carrying do MFDM. addition, uncovered requirement normal survival pre-implantation zygotes.