Jag2-flox Mouse

Jag2, short for jagged canonical Notch ligand 2, is a key ligand in the Notch signaling pathway. The Notch signaling pathway is involved in multiple cellular processes such as cell fate determination, proliferation, and apoptosis, which are crucial for embryonic development and tissue homeostasis [4,5].

In non-small cell lung cancer (NSCLC), deletion of Jag2 in cancer cells (a form of loss-of-function experiment) attenuated tumor growth and activated anti-tumor T cell responses. Jag2-deficient lung tumors had macrophages expressing immunostimulatory mediators, suggesting that Jag2 ablation promotes Nr4a-mediated induction of Notch ligands DLL1/4 on cancer cells, which in turn activates macrophage immunostimulatory functionality via Notch1/2 signaling [1].

In intervertebral disc degeneration (IVDD), recombinant JAG2 induced Notch2 and Hes1/Hey2 expression, promoting nucleus pulposus (NP) cell proliferation. Down-regulation of Notch2/Hes1/Hey2 led to G0/G1 phase cell cycle arrest in NP cells. Intradiscal injection of JAG2 alleviated IVDD in a rat model, indicating that JAG2/Notch2 inhibits IVDD by modulating cell proliferation, apoptosis, and extracellular matrix [2].

In ovarian cancer, JAG2+ tumor-associated neutrophils (TANs) enhanced Notch signaling activation, promoting the differentiation of naïve CD4+ T cells into effector regulatory T cells (eTregs), which hampers PD-1 blockade response. Pharmacological targeting of Notch signaling or JAG2 neutralization antibodies enhanced the efficacy of PD-1 monoclonal antibodies in xenograft and patient-derived tumor organoid models [3].

In summary, Jag2, through the Notch signaling pathway, plays important roles in various biological processes and disease conditions. Gene knockout or conditional knockout models, such as those in NSCLC, IVDD, and ovarian cancer, have revealed its functions in tumor growth regulation, cell proliferation, apoptosis, and immune evasion, providing insights into potential therapeutic strategies for these diseases.