YWHAE, also known as 14-3-3ε, is a gene located on chromosome 17p13.3. Its product, the 14-3-3epsilon protein, belongs to the 14-3-3 protein family. As a molecular scaffold, YWHAE participates in various biological processes such as cell adhesion, cell cycle regulation, signal transduction, and malignant transformation, and is involved in pathways like MAPK, NF-κB, and PI3K [2]. It is of great biological importance as it relates to numerous diseases [2]. Genetic models, especially mouse models, are valuable for studying YWHAE.

In a mouse knockout study of Ywhae, neuroanatomical studies revealed brain structural defects including thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus, paralleling the brain malformations seen in humans with YWHAE loss-of-function variants. These human cases showed manifestations like developmental delay, delayed speech, seizures, and brain malformations such as corpus callosum hypoplasia, delayed myelination, and ventricular dilatation, indicating that YWHAE loss-of-function causes a neurodevelopmental disease with brain abnormalities [1].

In conclusion, YWHAE is a crucial gene involved in multiple biological processes. The Ywhae knockout mouse model has been instrumental in revealing its role in neurodevelopmental diseases, specifically demonstrating that loss-of-function of YWHAE leads to brain abnormalities and associated neurological symptoms [1].

References:

1. Denommé-Pichon, Anne-Sophie, Collins, Stephan C, Bruel, Ange-Line, Faivre, Laurence, Yalcin, Binnaz. 2023. YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse. In Genetics in medicine : official journal of the American College of Medical Genetics, 25, 100835. doi:10.1016/j.gim.2023.100835. https://pubmed.ncbi.nlm.nih.gov/36999555/

2. Jin, Xi, Dai, Minhui, Zhou, Yanhong. . Genetic variation of YWHAE gene-"Switch" of disease control. In Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 47, 101-108. doi:10.11817/j.issn.1672-7347.2022.210394. https://pubmed.ncbi.nlm.nih.gov/35545369/