A Hypomorphic Lsd1 Allele Results in Heart Development Defects in Mice

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Title: A Hypomorphic Lsd1 Allele Results in Heart Development Defects in Mice
Author(s): Nicholson, TB
Singh, AK
Su, H
Hevi, S
Wang, J
Bajko, J
Li, M
Valdez, R
Goetschkes, M
Capodieci, P
Loureiro, J
Cheng, X
Li, E
Kinzel, B
Labow, M
Chen, T
Item Type: Journal Article
Abstract: Article Authors Metrics Comments Related Content Abstract Introduction Results Discussion Materials and Methods Supporting Information Acknowledgments Author Contributions References Reader Comments (0) Media Coverage (0) Figures Abstract Lysine-specific demethylase 1 (Lsd1/Aof2/Kdm1a), the first enzyme with specific lysine demethylase activity to be described, demethylates histone and non-histone proteins and is essential for mouse embryogenesis. Lsd1 interacts with numerous proteins through several different domains, most notably the tower domain, an extended helical structure that protrudes from the core of the protein. While there is evidence that Lsd1-interacting proteins regulate the activity and specificity of Lsd1, the significance and roles of such interactions in developmental processes remain largely unknown. Here we describe a hypomorphic Lsd1 allele that contains two point mutations in the tower domain, resulting in a protein with reduced interaction with known binding partners and decreased enzymatic activity. Mice homozygous for this allele die perinatally due to heart defects, with the majority of animals suffering from ventricular septal defects. Molecular analyses revealed hyperphosphorylation of E-cadherin in the hearts of mutant animals. These results identify a previously unknown role for Lsd1 in heart development, perhaps partly through the control of E-cadherin phosphorylation.
Publication Date: 24-Apr-2013
Date of Acceptance: 6-Mar-2013
URI: http://hdl.handle.net/10044/1/40012
DOI: http://dx.doi.org/10.1371/journal.pone.0060913
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 8
Issue: 4
Copyright Statement: © 2013 Nicholson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: General Science & Technology
MD Multidisciplinary
Publication Status: Published
Article Number: e60913
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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