CLDN18.2-knockout mouse model with pancreas specificity as well as construction method and application of CLDN18.2-knockout mouse model

Abstract

The invention discloses a mouse model with pancreas specific knockout CLDN18.2 as well as a construction method and application of the mouse model. According to the invention, a FloxP mouse capable of performing conditional knockout of CLDN18.2 is established by adopting a CRISPR / Cas9 technology, a No.1 exon is taken as a conditional knockout region, then the mouse is hybridized with a mouse containing a pancreatic specific promoter Pdx1-Cre, and then the hybridized mouse is hybridized with a KP model mouse to obtain the pancreatic CLDN18.2 specific knockout KPC mouse model. The pancreatic specific CLDN18.2 knockout mouse model constructed by the invention can be used as a model tool to be applied to mechanism research of occurrence and development of pancreatic cancer, or can be used as a model tool to be applied to screening of clinical drugs for treating pancreatic cancer and the like.

Description

technical field [0001] The invention relates to the construction of an animal model, in particular to a mouse model of pancreas-specific knockout of CLDN18.2, a construction method and application thereof, and belongs to the field of construction and application of a mouse model of pancreas-specific knockout of CLDN18.2. Background technique [0002] Pancreatic cancer, as the "king of cancers", has an insidious onset, is difficult to diagnose at an early stage, and is highly metastatic. More than 50% of patients will develop distant metastasis at the time of diagnosis or after diagnosis, losing the chance of radical cure and having a very poor prognosis. , the degree of malignancy is extremely high, and its five-year survival rate is less than 10%. Pancreatic cancer has an incidence rate of 3% in men and women, and a mortality rate of 8%, ranking fourth in the mortality rate of malignant tumors, second only to colorectal cancer. Surgery has become an important method for th...

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Problems solved by technology

[0002] Pancreatic cancer, as the "king of cancers", has an insidious onset, difficulty in early diagnosis, and is highly metastatic. More than 50% of patients will have distant metastasis at or after diagnosis, losing the chance of radical cure, and the prognosis is extremely poor , the degree of malignancy is extremely high, and its five-year survival rate is less than 10%.

[0005] Existing literature has reported C57BL / 6 mice that knockout Exon1 of CLDN18.2, but in these mouse models, the CLDN18.2 gene is systemically knocked out, and organ and tissue-specific knockout cannot be achieved, and No mouse model of pancreas-specific knockout of CLDN18.2 has been reported

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