In mice, BAF53b deletion results in perinatal lethality owing to a failure to nurse, and only one in ten survive to adulthood with hyperactivity phenotypes (Lessard et al., 2007; Wu et al., 2007). Interestingly, the brain of BAF53b−/− mice at postnatal day 0 (P0) does not differ appreciatively from wild-type in its size and complexity, indicating that intrinsic, activity-independent dendritogenesis is not affected (Wu et al., 2007). However, ex vivo cultures of BAF53b−/− hippocampal and cortical neurons reveal a striking deficit in the ability to elaborate dendritic processes following KCl stimulation. This phenotype can be rescued by the introduction of wild-type BAF53b, but not its homolog, BAF53a. BAF53a and BAF53b belong to the family of actin-related proteins (Arps) and contain actin folds with four distinct subdomains, the most divergent of which is subdomain 2. Remarkably, chimeric BAF53a containing the actin fold subdomain 2 of BAF53b was able to rescue the dendritic outgrowth phenotype of BAF53b-null, demonstrating that functional specificity is conferred by the structural divergence between homologous subunits.
