Junb-flox Mouse

JunB, a proto-oncogene, is a crucial member of the dimeric activator protein-1 (AP-1) complex. It plays significant roles in various physiological processes such as placental formation, cardiovascular development, myelopoiesis, angiogenesis, endochondral ossification, and epidermis tissue homeostasis. It is also involved in regulating innate and adaptive immune responses by influencing immune cell differentiation and cytokine secretion, and is implicated in tumorigenesis through controlling cell proliferation, differentiation, senescence, and metastasis [1].

In male mice, depletion of JunB in adipocytes increases the fraction of adipocytes with high thermogenic capacity, leading to enhanced energy expenditure and protection against diet-induced obesity and insulin resistance. JunB antagonizes the stimulatory effects of PPARγ coactivator-1α on high-thermogenic adipocyte formation [2].

In macrophage-specific JunB knockdown mice, inhibition of JunB blunts the administration time-dependent effect of ConA and attenuates liver injury, indicating JunB promotes macrophage inflammation through regulating AKT and extracellular signal-regulated kinase (ERK) signalling pathways [3].

In triple-negative breast cancer (TNBC), NAT10 upregulates JunB expression via increasing ac4C modification on its mRNA, and JunB further up-regulates LDHA expression to facilitate glycolysis and create an immunosuppressive tumor microenvironment [4].

In preeclampsia, interference with JUNB expression in macrophages promotes M2 polarization, which benefits trophoblast invasion, migration, and angiogenesis. JUNB regulates the MIIP/PI3K/AKT pathway [5].

In CAR-T cells, downregulation of JunB by MEK inhibition prevents cell exhaustion and terminal differentiation [6].

In T helper cells, Junb-deficient CD4+ T cells show impaired accumulation and increased sensitivity to apoptosis, and JunB directly inhibits apoptosis-related genes [7].

In a syngeneic spontaneous breast cancer metastasis model, stromal JUNB acts as a suppressor of distant metastasis, and its deficiency leads to increased influx of myeloid cells and upregulation of angiogenesis-promoting proteins in neutrophils [8].

In conclusion, JunB has diverse essential biological functions, playing a role in metabolism, immune responses, and tumorigenesis. Studies using gene knockout or conditional knockout mouse models have revealed its significance in specific disease areas such as obesity, liver injury, TNBC, preeclampsia, and breast cancer metastasis, enhancing our understanding of related biological processes and providing potential therapeutic targets.