p38 gamma MAPK12 CRISPR Activation Plasmid (m): sc-424361-ACT

Mapk12 encodes p38 gamma (MAPK12), a stress-activated mitogen-activated protein kinase that integrates extracellular cues to regulate transcriptional programs controlling cellular differentiation, metabolism, and survival. p38 gamma participates in MAPK signaling networks downstream of inflammatory cytokines and environmental stress, influencing phosphorylation cascades that shape gene expression and cytoskeletal dynamics. In mouse systems, MAPK12 activity has been linked to tissue-specific responses in skeletal muscle and immune-relevant signaling, making it useful for studying stress adaptation and context-dependent kinase crosstalk. Dysregulated p38 pathway signaling is frequently examined in models of inflammation, metabolic imbalance, and cancer-associated signaling rewiring, where MAPK12 can act as a node that modulates pathway amplitude and specificity.

p38 gamma MAPK12 CRISPR Activation Plasmid (m) provides a targeted, non-destructive approach to upregulating endogenous Mapk12 expression without altering the underlying DNA sequence.

p38 gamma MAPK12 CRISPR Activation Plasmid (m) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the Mapk12 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 Mapk12 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous p38 gamma MAPK12 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native Mapk12 locus and enabling the study of p38 gamma MAPK12-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of p38 gamma MAPK12 pathway restoration in tumor cells with silenced or reduced Mapk12 expression.

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