Impaired memory and marble burying activity in deformed epidermal autoregulatory factor 1 (Deaf1) conditional knockout mice

• Published in: Behavioural brain research Vol. 380; p. 112383
• Main Authors: McGee, Stacey R., Rose, Gregory M., Jensik, Philip J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17-02-2020
• Subjects: Animals; Anxiety; Behavior, Animal - physiology; Conditioning, Classical - physiology; DAND; Development; Disease Models, Animal; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Hippocampus; Hippocampus - pathology; Learning; Male; Maze Learning - physiology; Memory; Memory Disorders - genetics; Memory Disorders - physiopathology; Mice; Mice, Knockout; Transcription Factors - genetics; Transcription Factors - physiology; Learning; Development; Anxiety; DAND; Memory; Hippocampus
• DOI: 10.1016/j.bbr.2019.112383
• EISSN: 1872-7549
• ISSN: 0166-4328

•Deaf1 expression is involved in contextual fear and spatial memory.•Conditional deletion of Deaf1 decreases marble burying activity.•Dorsal hippocampal area is reduced in mice lacking Deaf1.
Deleterious mutations within the DNA binding domain of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of neurodevelopmental disorders including intellectual disabilities and autism spectrum disorders. While whole animal deletion of Deaf1 in mice is lethal, mice with conditional disruption of the gene in neuronal precursor cells can display memory deficits and increased anxiety-like behavior. This study aimed to further characterize learning and memory alterations and assess changes in marble burying activity and hippocampal size in mice with conditional deletion of Deaf1. Mice lacking DEAF1 in the CNS (NKO) displayed reduced memory in both contextual fear conditioning and a 3-day massed trials Morris water maze paradigm. NKO mice had reduced marble burying activity in full cage marble burying tests. Using a half-cage marble test, NKO mice again buried fewer marbles and spent significantly more time on the side of the cage away from the marbles compared to control animals. The area of the dorsal hippocampus of NKO mice was decreased compared to control and animals with a single Deaf1 allele. These results continue to establish the importance of DEAF1 in cognitive behavior and provide new evidence that DEAF1 regulates hippocampal morphology.