title: A hypomorphic lsd1 allele results in heart development defects in mice.
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.
authors: Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, United States of America.
authors: Thomas B
authors: TB
authors: Nicholson
authors: Anup K
authors: AK
authors: Singh
authors: Hui
authors: H
authors: Su
authors: Sarah
authors: S
authors: Hevi
authors: Jing
authors: J
authors: Wang
authors: Jeff
authors: J
authors: Bajko
authors: Mei
authors: M
authors: Li
authors: Reginald
authors: R
authors: Valdez
authors: Margaret
authors: M
authors: Goetschkes
authors: Paola
authors: P
authors: Capodieci
authors: Joseph
authors: J
authors: Loureiro
authors: Xiaodong
authors: X
authors: Cheng
authors: En
authors: E
authors: Li
authors: Bernd
authors: B
authors: Kinzel
authors: Mark
authors: M
authors: Labow
authors: Taiping
authors: T
authors: Chen
mesh_terms: D000483:Alleles; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006345:Heart Septal Defects, Ventricular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D056466:Histone Demethylases; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011247:Pregnancy; D011485:Protein Binding
chemical_list: D015820:Cadherins; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating
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