Baz2b-KO Mouse

BAZ2B, also known as bromodomain adjacent to zinc finger 2B, is a regulatory subunit of the ISWI (Imitation Switch) remodeling complex and is involved in nucleosome remodeling [1]. It is a large multidomain protein containing epigenetic reader domains like the plant homeodomain (PHD), bromodomain (BRD), and a Tip5/ARBP/MBD (TAM) domain. BAZ2B has been implicated in various biological processes and diseases, playing a significant role in chromatin-related functions.

Loss-of-function and haploinsufficiency of BAZ2B are associated with multiple diseases. In humans, heterozygous loss-of-function variants in BAZ2B cause an autosomal dominant neurodevelopmental syndrome with incomplete penetrance. Phenotypes associated with BAZ2B loss-of function include developmental delay, intellectual disability, autism spectrum disorder, speech delay, behavioral abnormalities, seizures, vision-related issues, congenital heart defects, poor fetal growth, and dysmorphic features [2]. In mice, ablation of Baz2b, the mouse orthologue of human BAZ2B, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice, suggesting its role in healthy ageing [3]. In the context of liver regeneration, in vivo CRISPR screening identified Baz2b as a regulator, with inhibition of Baz2b promoting liver regeneration. Distinct BAZ2-specific bromodomain inhibitors also led to accelerated liver healing after injuries and improved healing in an inflammatory bowel disease model [4]. In children with asthma, lnc-BAZ2B promotes M2 macrophage activation and inflammation by stabilizing BAZ2B pre-mRNA, and knockdown of Baz2b alleviated asthma severity in a mouse model [5]. Depletion of Baz2B in the Hap1 cell line resulted in altered cell morphology, reduced colony formation, and perturbed transcriptional profiles, though overall chromatin structure remained unchanged [6].

In conclusion, BAZ2B is crucial in processes such as neurodevelopment, healthy ageing, tissue regeneration, and inflammation. Research on BAZ2B, especially through gene knockout and other loss-of-function models in mice and in vitro cell studies, has provided insights into its role in various disease conditions like neurodevelopmental disorders, age-related cognitive decline, liver regeneration-related pathologies, and asthma. This understanding of BAZ2B's functions can potentially contribute to the development of therapeutic strategies for these diseases.