Postnatal Cranial Characterization in a Mouse Model of Cortex‐Specific Overexpression of BAF170

Abstract

The BRG1/BRM-associated factor (BAF) chromatin remodeling complexes are composed of the mutually exclusive brahma or brahma-related gene 1 ATPases, along with several other structural subunits and their isoforms. BAF complexes serve specific functions in widely different cell types and developmental processes. Mammalian BAF170, a subunit of chromatin remodeling complex mSWI/SNF, is an intrinsic factor controlling cortical size. It was previously reported that conditional deletion of BAF170 promotes indirect neurogenesis by increasing the pool of intermediate progenitors and results in an enlarged cortex, whereas cortex specific BAF170 overexpression results in a smaller cortex. However, the influence of cortex specific BAF170 overexpression on size and shape of the craniofacial complex, specifically the skull, is not well understood. We hypothesized that the skull phenotype of mice with cortex specific BAF170 overexpression may include indirect effects of the reduced cortex including reduced intracranial volume and linear distance measures of the skull relative to unaffected littermates. To further understand the influence of cortex-specific conditional overexpression of BAF170 on the cranial phenotype of young mice, we examined two postnatal ages of the cortex specific BAF170 overexpression mouse model. Here, we combine measures of gross observation (body weight, body length, brain weight) and of 3D micro-computed tomography imaging of the head (overall skull length, cranial length, cranial height, cranial width, intracranial volume) at 28 (P28; N=6) and 42 (P42; N=12) days of age to assess the influence of BAF170 overexpression on skull morphology as compared to unaffected littermates. In our small sample, gross examination of the brain indicated an obviously distinctive brain morphological phenotype at both ages, including a visibly smaller cortex, in mice with overexpression of BAF170. Results showed few other differences at P28, although brain weight and skull width were reduced in mice with cortex specific BAF170 overexpression as compared to unaffected littermates. By P42, brain weight was no longer different between the genotypes, but cranial length, width, and height were all smaller. Additionally, intracranial volume was reduced in mice overexpressing BAF170 at P42. These results suggest that BAF170 overexpression in mice, which specifically supervises development of a smaller cortex, affects their skull phenotype in terms of size and possibly shape at P28 and P42, with potentially increased differences occurring with age. Further morphometric exploration is necessary to determine whether additional craniofacial differences exist at other ages.