Homer-1 CRISPR Activation Plasmid (m): sc-424092-ACT

Mouse Homer1 encodes Homer-1, a postsynaptic density scaffolding protein that organizes group I metabotropic glutamate receptors and associated effectors to coordinate calcium signaling, synaptic plasticity, and activity-dependent gene programs. Through its EVH1-mediated interactions, Homer-1 couples mGluR1/5 to IP3 receptor–dependent calcium release and interfaces with Shank and other PSD components to shape excitatory synapse architecture. Altered HOMER1 signaling has been linked to dysregulated glutamatergic neurotransmission and circuit remodeling in neuropsychiatric and neurodegenerative disease contexts, including stress-related phenotypes and seizure susceptibility. As an immediate early gene isoform and long-form scaffold, Homer-1 provides a tractable node for studying stimulus-dependent synaptic adaptation and receptor trafficking.

Homer-1 CRISPR Activation Plasmid (m) provides a targeted, non-destructive approach to upregulating endogenous Homer1 expression without altering the underlying DNA sequence.

Homer-1 CRISPR Activation Plasmid (m) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the Homer1 locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the Homer1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous Homer-1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native Homer1 locus and enabling the study of Homer-1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of Homer-1 pathway restoration in tumor cells with silenced or reduced Homer1 expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.