Bicra-KO Mouse

Bicra, also known as GLTSCR1, encodes a subunit of the non-canonical BAF (ncBAF) chromatin remodeling complex, which is involved in various biological processes related to chromatin regulation. The ncBAF complex is part of the SWI/SNF family, playing a crucial role in gene expression regulation and thus influencing many cellular functions and developmental processes [1].

In humans, rare variants in Bicra (10 loss-of-function, 2 missense) were identified in 12 individuals, leading to neurodevelopmental phenotypes such as developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities, as well as dysmorphic features. However, the majority lacked the fifth digit/nail hypoplasia typical of most SWI/SNF-related intellectual disability disorders [1]. In zebrafish, a mutation mimicking a loss-of-function variant caused craniofacial defects, similar to the dysmorphic facial features in humans with Bicra variants [1]. In Drosophila, loss of Bicra function led to impaired courtship learning and choice abilities, with its function in neurons of the mushroom body being responsible for these behaviors [2]. In mice, homozygous loss of Bicra led to small, pale pups that died within 24 hours after birth, with blood-related defects including defective erythroblastic islands and irregularly sized red blood cells, due to a defect in fetal liver macrophages involved in erythrocyte maturation [5].

In conclusion, Bicra plays a vital role in neurodevelopment, as demonstrated by human genetic studies and model organism research. The loss-of-function experiments in zebrafish, Drosophila, and mice have revealed its role in craniofacial development, cognitive behaviors, and fetal liver macrophage function respectively, providing insights into related human diseases such as Coffin-Siris syndrome 12 and other neurodevelopmental disorders [1,2,3,4,5].

References:

1. Barish, Scott, Barakat, Tahsin Stefan, Michel, Brittany C, Scott, Daryl A, Bellen, Hugo J. 2020. BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms. In American journal of human genetics, 107, 1096-1112. doi:10.1016/j.ajhg.2020.11.003. https://pubmed.ncbi.nlm.nih.gov/33232675/

2. Sun, Ying, Li, Zhuojie, Li, Wenzhe, Xue, Lei. 2021. Loss of Bicra impairs Drosophila learning and choice abilities. In Neuroscience letters, 769, 136432. doi:10.1016/j.neulet.2021.136432. https://pubmed.ncbi.nlm.nih.gov/34974109/

3. Tu, Youquan, Fang, Chunyan, Xu, Jian, Liang, Mengmeng, Yang, Zuozhen. 2023. A de novo variant of BICRA results in Coffin-Siris syndrome 12. In Molecular genetics & genomic medicine, 11, e2250. doi:10.1002/mgg3.2250. https://pubmed.ncbi.nlm.nih.gov/37485815/

4. Asadauskaitė, Greta, Morkūnienė, Aušra, Utkus, Algirdas, Burnytė, Birutė. 2022. Identification of a novel BICRA variant leading to the newly described Coffin-Siris syndrome 12. In Brain & development, 45, 185-190. doi:10.1016/j.braindev.2022.11.003. https://pubmed.ncbi.nlm.nih.gov/36437209/

5. Sood, Surbhi, Alpsoy, Aktan, Jiao, Guanming, Hutchcroft, Jill, Dykhuizen, Emily. 2024. Loss of Bicra/Gltscr1 leads to a defect in fetal liver macrophages responsible for erythrocyte maturation in mice. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.10.17.618940. https://pubmed.ncbi.nlm.nih.gov/39464106/