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|Title:||GENETICALLY MANIPULATING NUCLEAR ENVELOPE PROTEIN, NESPRIN 1||Authors:||LEONG EI LEEN||ORCID iD:||orcid.org/0000-0002-8072-4468||Keywords:||Nesprin1, LINC complex||Issue Date:||12-Dec-2017||Citation:||LEONG EI LEEN (2017-12-12). GENETICALLY MANIPULATING NUCLEAR ENVELOPE PROTEIN, NESPRIN 1. ScholarBank@NUS Repository.||Abstract:||KASH-domain proteins, such as Nesprin-1 (Nesp1), localize to the outer nuclear membrane of the nuclear envelope (NE). By interacting with SUN domain proteins, which localize to the inner nuclear membrane of the NE, they form the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex that tethers the nucleus to the cytoskeleton. Underlying the NE is the lamina, composed of lamins A, C, B1 and B2, that helps anchor the LINC complex to the NE. Here I describe the derivation of 7 Nesp1 mouse lines, in particular, one expressing a KASHless form of Nesp1. This mutant form of Nesp1 fails to localize to the NE. In the Lmna null mice, which die from cardiomyopathy, expression of this KASHless form of Nesp1 significantly extends the lifespan of the Lmna null mice. Breaking the LINC complex decreases the mechanical strain placed on the weakened nucleus in the Lmna null mice, so prevents heart failure.||URI:||http://scholarbank.nus.edu.sg/handle/10635/147494|
|Appears in Collections:||Ph.D Theses (Open)|
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