Back to Search
Start Over
Neuroanatomy and Behaviour in Mice with a Haploinsufficiency of AT-Rich Interactive Domain 1B (ARID1B) Throughout Development
- Publication Year :
- 2020
-
Abstract
- One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification, and genes that regulate chromatin modify and control events regulating the formation of neural connections. AT-Rich Interactive Domain 1B (ARID1B) , a chromatin modifier, has been shown to be reduced in autism spectrum disorder (ASD) and to affect rare and inherited genetic variation in a broad set of NDDs. For this work, a novel preclinical mouse model of Arid1b deficiency was created and molecularly validated to characterize and define neuroanatomical, behavioural and transcriptional phenotypes. Brains of adult Arid1b +/- mice had a smaller cerebellum along with a larger hippocampus and corpus callosum. In addition, a notable sex dependence was observed throughout development; males had an early emergence of the neuroanatomical phenotype around postnatal day 7, whereas females had a delayed emergence of the phenotype around postnatal day 40. Behavioural assays relevant to NDD were conducted during neonatal development and adulthood to evaluate general health, anxiety-like, motor, cognitive, and social behaviours in Arid1b +/- mice. During neonatal development, Arid1b +/- mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. As adults, Arid1b +/- mice showed low motor skills in open field exploration and normal three chambered approach. Arid1b +/- mice had learning and memory deficits in novel object recognition but surprisingly not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviours were observed. This study represents a full investigation of Arid1b +/- haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.
Details
- Database :
- OAIster
- Notes :
- application/pdf
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1287303207
- Document Type :
- Electronic Resource