ADCY10 Knockout Cell Line (HEK293)

The choice depends on whether you are studying ADCY10 (soluble adenylyl cyclase, sAC, SAC, AC10)'s role as the only known mammalian CO₂/HCO₃⁻-activated cyclase or modeling its functions in sperm capacitation and emerging bicarbonate signaling research. The Knockout line is the standard tool for asking whether sAC is required for these processes — ADCY10/sAC is fundamentally different from the nine other mammalian adenylyl cyclases (ADCY1-9, transmembrane AC isoforms activated by Gs-coupled GPCRs); sAC is a soluble cytoplasmic enzyme directly activated by bicarbonate (HCO₃⁻) and calcium, generating cAMP independently of GPCR signaling; sAC is critical for sperm capacitation (the maturation process required for fertilization), and has emerging roles in mitochondrial function, autophagy, and cardiac arrhythmias. Overexpression is useful for studying sAC gain-of-function effects. For bicarbonate signaling research, the EDITGENE ADCY10 Knockout in HEK293 enables study of sAC biology. Rescue with wild-type or catalytically-dead sAC enables structure-function studies. The knockout is a critical specificity tool for ⭐ LRE1 and KH7 (selective sAC inhibitors), emerging sAC inhibitors for non-hormonal male contraception (sAC inhibition blocks sperm capacitation; TDI-11861 sAC inhibitor showed promising preclinical contraception activity 2023), and emerging sAC-targeted therapeutic approaches.

Primary applications: • Bicarbonate-induced cAMP: HCO₃⁻-induced cAMP elevation analysis in sAC-null cells — should be completely abolished given sAC is the only HCO₃⁻-responsive cyclase. • Sperm capacitation modeling: in heterologous reproductive biology contexts, sAC's role in sperm capacitation given male contraception applications. • sAC inhibitor specificity: critical genetic control for ⭐ LRE1, KH7 (classical sAC inhibitors), and ⭐ TDI-11861 (emerging on-demand non-hormonal male contraception candidate). • Mitochondrial cAMP: in heterologous mitochondrial-relevant contexts, sAC's mitochondrial functions in OXPHOS regulation. EDITGENE recommends this model for researchers investigating bicarbonate signaling, sperm biology, and emerging sAC inhibitor-based non-hormonal male contraception (a major emerging therapeutic area).

Yes. sAC rescue experiments require attention to the soluble cyclase architecture: • Construct design: use a codon-modified ADCY10 sequence with a small C-terminal tag (FLAG, HA). sAC has tandem cyclase domains (C1, C2) forming the active site, plus regulatory regions — preserve all elements; note that full-length sAC exists alongside multiple shorter isoforms (sACt, soluble truncated forms) that retain catalytic activity. • Catalytically-dead rescue: active site metal-binding aspartate mutations abolish cyclase activity. • Bicarbonate-insensitive rescue: HCO₃⁻-binding site mutations separate bicarbonate sensing from catalytic activity. • Functional readout: rescue should restore HCO₃⁻-induced cAMP elevation. HEK293 transduces efficiently with lentivirus and supports stable rescue line generation.