Arid1b-KO Mouse

ARID1B, encoding AT-rich interactive domain-containing protein 1B, is a DNA-binding subunit of the Brahma-associated factor chromatin remodelling complexes [2]. These complexes play a key role in regulating gene activity, and ARID1B is thought to be part of a neuron-specific chromatin remodelling complex involved in the regulation of stem/progenitor cells differentiating into post-mitotic neurons [2]. Mouse models of Arid1b haploinsufficiency have been crucial for understanding its function [1,4].

In mice, Arid1b heterozygous deletion leads to severe behavioral abnormalities similar to autism spectrum disorders and intellectual disability, along with marked changes in gene expression, decreased body size, and a cortical excitatory/inhibitory imbalance due to altered GABAergic neuron numbers and impaired inhibitory synaptic transmission [4]. Treating adult Arid1b mutant mice with a positive GABA allosteric modulator rescues multiple behavioral abnormalities, while recombinant mouse growth hormone only increases body size without affecting aberrant behavior [4]. Additionally, in a mouse incisor model, loss of Arid1b in the GLI1+ mesenchymal stem cell (MSC) lineage disturbs MSCs' quiescence and leads to their proliferation through the ectopic activation of non-canonical Activin signaling via p-ERK [3].

In conclusion, ARID1B is vital in neurodevelopment and maintaining MSC homeostasis. Mouse models of Arid1b haploinsufficiency have revealed its role in neural development and behavior, as well as in stem cell regulation, contributing to our understanding of related neurodevelopmental disorders such as intellectual disability and autism spectrum disorder [1,3,4].

References:

1. Moffat, Jeffrey J, Smith, Amanda L, Jung, Eui-Man, Ka, Minhan, Kim, Woo-Yang. 2021. Neurobiology of ARID1B haploinsufficiency related to neurodevelopmental and psychiatric disorders. In Molecular psychiatry, 27, 476-489. doi:10.1038/s41380-021-01060-x. https://pubmed.ncbi.nlm.nih.gov/33686214/

2. Sim, Joe C H, White, Susan M, Lockhart, Paul J. . ARID1B-mediated disorders: Mutations and possible mechanisms. In Intractable & rare diseases research, 4, 17-23. doi:10.5582/irdr.2014.01021. https://pubmed.ncbi.nlm.nih.gov/25674384/

3. Zhang, Mingyi, Guo, Tingwei, Pei, Fei, Sehgal, Prerna, Chai, Yang. 2024. ARID1B maintains mesenchymal stem cell quiescence via inhibition of BCL11B-mediated non-canonical Activin signaling. In Nature communications, 15, 4614. doi:10.1038/s41467-024-48285-2. https://pubmed.ncbi.nlm.nih.gov/38816354/

4. Moffat, Jeffrey J, Jung, Eui-Man, Ka, Minhan, Santen, Gijs W E, Kim, Woo-Yang. 2018. The role of ARID1B, a BAF chromatin remodeling complex subunit, in neural development and behavior. In Progress in neuro-psychopharmacology & biological psychiatry, 89, 30-38. doi:10.1016/j.pnpbp.2018.08.021. https://pubmed.ncbi.nlm.nih.gov/30149092/