Nde1-KO Mouse

Nde1, also known as Nuclear Distribution Element 1 or NudE, is a crucial protein in multiple biological processes. It is an important binding partner of cytoplasmic dynein-1, a microtubule minus-end directed molecular motor. Nde1, along with Lis1, facilitates the assembly of dynein with dynactin and a cargo adaptor in an active transport complex, playing a key role in dynein-mediated transport pathways [1,2,3]. It is essential for brain development, and its abnormal function is associated with neurodevelopmental and psychiatric disorders [4].

Genetic studies in various models have provided insights into Nde1's functions. In zebrafish, nde1 homologous deficiency (nde1 -/-) leads to increased neurological apoptotic responses in early infancy, enlarged ventricles, shrank valvula cerebelli in adults, and autism-like behavior traits, revealing its role in normal neurological development [6]. In neocortical neurons, Nde1 loss-of-function (LOF) results in nuclear architecture aberrations, DNA double-strand breaks, and instability of pericentromeric satellite repeats, suggesting its importance in heterochromatin compaction and stability [5].

In conclusion, Nde1 is essential for processes like dynein-mediated transport, neurogenesis, and heterochromatin regulation. Studies using gene knockout models, such as the nde1 -/- zebrafish, have revealed its significance in normal neurological development and its association with neurodevelopmental and psychiatric disorders, offering valuable insights into the underlying disease mechanisms [5,6].

References:

1. Garrott, Sharon R, Gillies, John P, DeSantis, Morgan E. 2022. Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport. In Frontiers in cell and developmental biology, 10, 871935. doi:10.3389/fcell.2022.871935. https://pubmed.ncbi.nlm.nih.gov/35493069/

2. Zhao, Yuanchang, Oten, Sena, Yildiz, Ahmet. 2023. Nde1 promotes Lis1-mediated activation of dynein. In Nature communications, 14, 7221. doi:10.1038/s41467-023-42907-x. https://pubmed.ncbi.nlm.nih.gov/37940657/

3. Zhao, Yuanchang, Oten, Sena, Yildiz, Ahmet. 2023. Nde1 Promotes Lis1-Mediated Activation of Dynein. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.05.26.542537. https://pubmed.ncbi.nlm.nih.gov/37292665/

4. Bradshaw, Nicholas J, Hayashi, Mirian A F. 2016. NDE1 and NDEL1 from genes to (mal)functions: parallel but distinct roles impacting on neurodevelopmental disorders and psychiatric illness. In Cellular and molecular life sciences : CMLS, 74, 1191-1210. doi:10.1007/s00018-016-2395-7. https://pubmed.ncbi.nlm.nih.gov/27742926/

5. Chomiak, Alison A, Guo, Yan, Kopsidas, Caroline A, Doughty, Martin L, Feng, Yuanyi. 2022. Nde1 is required for heterochromatin compaction and stability in neocortical neurons. In iScience, 25, 104354. doi:10.1016/j.isci.2022.104354. https://pubmed.ncbi.nlm.nih.gov/35601919/

6. Zhang, Qi, Li, Tingting, Lin, Jia, Wang, Xu, Li, Qiang. 2022. Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior. In iScience, 25, 103876. doi:10.1016/j.isci.2022.103876. https://pubmed.ncbi.nlm.nih.gov/35243238/