title: Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviors in aged mice.
abstract: The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation, and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviors. Using both Grhl3-knockout mice (Grhl3-/-), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3flox/flox), they performed histological expression analyses and behavioral tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety, and stress. They found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain; however, aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviors suggestive of decreased fear and anxiety. They conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behavior or hyperactivity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 775-788, 2017.
authors.affiliation: Department of Medicine, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dworkin
authors.affiliation: Department of Medicine, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.
authors.forename: Alana
authors.initials: A
authors.lastname: Auden
authors.affiliation: Department of Medicine, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.
authors.forename: Darren D
authors.initials: DD
authors.lastname: Partridge
authors.affiliation: Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Daglas
authors.affiliation: Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Medcalf
authors.affiliation: Department of Pathology, University of Melbourne, Parkville, Victoria, 3050, Australia.
authors.forename: Theo
authors.initials: T
authors.lastname: Mantamadiotis
authors.affiliation: Department of Medicine, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.
authors.forename: Smitha R
authors.initials: SR
authors.lastname: Georgy
authors.affiliation: Peter MacCallum Cancer Centre, The Victorian Comprehensive Cancer Centre, Parkville, Victoria, 3050, Australia.
authors.forename: Charbel
authors.initials: C
authors.lastname: Darido
authors.affiliation: Department of Medicine, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.|Department of Hematology, Alfred Hospital, Prahran, Victoria, 3181, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Jane
authors.affiliation: Department of Medicine, Monash University Central Clinical School, Prahran, Victoria, 3181, Australia.|Department of Hematology, Alfred Hospital, Prahran, Victoria, 3181, Australia.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Ting
mesh_terms: D000375:Aging; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D005518:Food Preferences / Q000523:psychology; D005684:Gait / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008124:Locomotion / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C499942:Grhl3 protein, mouse; D019394:Ki-67 Antigen; C577485:Nes protein, mouse; D064231:Nestin; D013549:Sweetening Agents; D014157:Transcription Factors; D013395:Sucrose
keywords: Cre-mediated deletion; Grainyhead-like; habenula