Hsp90ab1 Knockout BV-2 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population generated by disruption of the mouse Hsp90ab1 gene in the BV-2 microglial cell line. This product provides a mixed knockout pool, offering a population-level loss-of-function model to study Hsp90??-dependent cellular functions. The genetic disruption abrogates expression of the constitutively active Hsp90?? chaperone, enabling investigation of its role in protein homeostasis and signal transduction without clonal selection bias.
The parental BV-2 cell line is an immortalized mouse microglial line derived from C57BL/6 mice, transformed with v-raf and v-myc oncogenes. BV-2 cells recapitulate key microglial functions, including immune surveillance, phagocytosis, and secretion of inflammatory mediators, and are widely used as a model of neuroinflammation and microglial activation. Their robust growth and responsiveness to stimuli make them suitable for mechanistic studies of innate immune signaling in the central nervous system.
Hsp90ab1 encodes the Hsp90?? chaperone, which is constitutively expressed and essential for the folding, stabilization, and activation of numerous client proteins. Hsp90?? functions within a multichaperone complex that includes Hsp70, HOP (Stip1), p23 (PTGES3), CDC37, and immunophilins such as FKBP5. Key client proteins stabilized by Hsp90?? include Akt, Raf, IKK, the glucocorticoid receptor, p53, and eNOS. Consequently, Hsp90?? intersects with multiple signaling networks: it is necessary for PI3K-AKT and MAPK/ERK pathway propagation, NF-??B activation, and steroid hormone receptor signaling. Upstream, Hsp90ab1 expression is induced by heat shock factor 1 (HSF1) in response to proteotoxic stress, as well as by growth factors (EGF, PDGF) and inflammatory cytokines (TNF-??, IL-1??), linking chaperone capacity to cellular stress and immune cues.
Disruption of Hsp90?? in BV-2 microglia critically impairs chaperone-assisted maturation of signaling proteins that control inflammatory and survival responses. Without functional Hsp90??, client kinases such as Akt and Raf become destabilized, attenuating PI3K-AKT and MAPK/ERK signaling cascades. Additionally, deficient IKK stabilization dampens NF-??B pathway activation, potentially reducing pro-inflammatory cytokine production. This knockout model thus allows dissection of Hsp90??’s role in microglial activation, stress adaptation, and neuroprotective or neurotoxic phenotypes associated with chronic inflammation and protein aggregation.
This polyclonal knockout cell population is suited for a range of experimental applications, including characterization of Hsp90 client protein stability by Western blotting, transcriptional profiling of chaperone and inflammatory genes via RT-qPCR, and functional assays such as phagocytosis and cytokine secretion (ELISA). Phospho-signaling analysis can map altered pathway activities, while Hsp90 inhibitor sensitivity assays provide a platform for drug target validation and screening of novel chaperone inhibitors. The model supports research into neurodegenerative diseases, neuroinflammatory disorders, and cancer-related signaling, offering a physiologically relevant context to study chaperone biology in immune cells. For detailed protocols or custom services, please contact Ascent Research.
