HIF1A: It coordinates cellular metabolic reprogramming under hypoxic conditions to help cells adapt to the low-oxygen environment.

• Gene Information:  HIF is a transcription factor that is instrumental in the ability of cells to sense and adapt to changes in oxygen levels.
• Signaling Pathway: In a hypoxic environment, the accumulation of HIF1a can regulate the expression of downstream genes through a variety of mechanisms, promoting tumor cell proliferation, angiogenesis, energy metabolism, epitheliale-mesenchymal transition (EMT), and immune escape, etc., thereby making tumor cells more tolerant to HME and acquiring the greater capacity for proliferation, metastasis, and invasion.
• Therapeutic Inhibition: Given its roles in tumors and inflammation, developing antagonists to modulate immune function holds promise for inhibiting tumor growth.

HIF1A

• The exons 1-15 of mouse Hif1α gene are replaced by human counterparts in B-hHIF1A mice.
• The promoter and 5’UTR region of the mouse gene are retained, but the 3’UTR region of the mouse gene are replaced by human counterparts.
• The human HIF-1α expression is driven by endogenous mouse Hif-1α promoter, while mouse Hif-1α gene transcription and translation will be disrupted.

Strain specific analysis of HIF1A mRNA expression in wild-type C57BL/6JNifdc mice and B-hHIF1A mice by RT-PCR. Testis RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hHIF1A mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human HIF1A primers. Mouse Hif1a mRNA was only detectable in wild-type mice. Human HIF1A mRNA was exclusively detectable in homozygous B-hHIF1A mice but not in wild-type mice.

Western blot analysis of HIF1A protein expression in homozygous B-hHIF1A mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hHIF1A mice (H/H), and then analyzed by western blot with anti-HIF1A antibody (abcam, ab51608， the antibody was cross-reactive between human and mouse). 40 μg total proteins were loaded for western blotting analysis. （DMOG is a small-molecule compound. It inhibits prolyl hydroxylases (PHD) to block the degradation of HIF-1α, thereby stabilizing HIF-1-related genes.）