B-KPC mice: KRAS^G12D activation promotes oncogenic signaling, while TP53^R172H disrupts tumor suppression. Their cooperation drives pancreatic tumor initiation and progression.

• Gene Information: KRAS encodes a small GTPase, while TP53 encodes a key tumor suppressor. KRAS^G12D and TP53^R172H are major genetic drivers of PDAC. 
• Protein Expression: KRAS is a membrane-associated signaling protein, whereas p53 is a stress-responsive nuclear transcription factor. KRAS^G12D remains constitutively active, while mutant p53 loses tumor-suppressive activity. 
• Signaling Pathway: Activated KRAS drives the RAF–MEK–ERK and PI3K–AKT pathways to promote proliferation and survival. TP53 dysfunction impairs cell-cycle arrest and apoptosis. 
• Model application : KRAS^G12D inhibition suppresses oncogenic signaling and tumor growth. TP53-associated vulnerabilities provide additional opportunities for synthetic-lethal therapeutic strategies.

B-KPC mice 

• A targeting vector was designed to place a G12D point mutation in exon 2 of the Kras gene, the loxP-flanked STOP element is located upstream of point mutations. The stop cassette prevents the expression of mutant Kras until it is removed by Cre mediated recombination of the Loxp sites, thus allowing expression of oncogenic Kras. 
• A targeting vector was designed to place a R172H point mutation in exon 5 of the Trp53 gene, the loxP-flanked STOP element is located upstream of point mutations. The stop cassette prevents the expression of mutant Trp53 until it is removed by Cre mediated recombination of the loxP sites, thus allowing expression of oncogenic Trp53. 
• The Pdx-driven expression cassette enables tissue-specific expression of Cre recombinase in the pancreas, excising the "Stop" sequence flanked by a pair of loxP sites, thereby initiating the expression of the Kras*G12D and Trp53*R172H genes

H&E staining of pancreas tissues in B-KPC mice. Pancreas tissues of C57BL/6 mice (+/+) (Female, 10w, 16w, 18w, n=3) and B-KPC mice (H/+) (Female, 10w, 16w, 18w, n=3) were collected and analyzed with H&E staining.

H&E staining of lung tissues in B-KPC mice. Lung tissues of C57BL/6 mice (+/+) (Female, 10w, 16w, 18w, n=3) and B-KPC mice (H/+) (Female, 10w, 16w, 18w, n=3) were collected and analyzed with H&E staining.

H&E staining of liver tissues in B-KPC mice. Liver tissues of C57BL/6 mice (+/+) (Female, 10w, 16w, 18w, n=3) and B-KPC mice (H/+) (Female, 10w, 16w, 18w, n=3) were collected and analyzed with H&E staining.