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A Hypomorphic Lsd1 Allele Results in Heart Development Defects in Mice.

Authors :
Nicholson, Thomas B.
Singh, Anup K.
Su, Hui
Hevi, Sarah
Wang, Jing
Bajko, Jeff
Li, Mei
Valdez, Reginald
Goetschkes, Margaret
Capodieci, Paola
Loureiro, Joseph
Cheng, Xiaodong
Li, En
Kinzel, Bernd
Labow, Mark
Chen, Taiping
Source :
PLoS ONE. Apr2013, Vol. 8 Issue 4, p1-14. 14p.
Publication Year :
2013

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
4
Database :
Academic Search Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
87677847
Full Text :
https://doi.org/10.1371/journal.pone.0060913