ISWI ATP-ases, Smarca5 and Smarca1, are required for normal murine neocortical development

Chromatin remodeling complexes modulate DNA accessibility permitting neuronal progenitor cells to proliferate and differentiate to form the mammalian neocortex. Smarca5 and Smarca1 are the ISWI ATP-ase proteins, within a variety of chromatin remodelling complexes. We created a mouse model with a truncated Smarca1, which inactivates the ATPase nucleosome rearranging activity of the protein. Secondly, using the cre/loxp system, we conditionally removed exon 5 of the Smarca5 gene, resulting in a null allele solely in the cortex of the mouse. Ultimately, we knockout (KO) both the Smarca5 and Smarca1 genes to analyze neocortical neurogenesis at E13.5 and identify their cooperative role during embryonic brain development. The DKO mice reveal significant forebrain hypoplasia. Overall design: Smarca5 and Smarca1 DKO, Smarca1 KO and WT E13.5 cortical samples. All are forebrain whole tissue mRNA stranded libraries.