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A mouse model for high-efficient Flp-recombinase-mediated genetic manipulation in the pancreas. | LitMetric

AI Article Synopsis

  • The study introduces a new genetic manipulation method using FLPo for pancreatic research, which complements the existing Cre recombinase system.
  • Researchers created transgenic mice with a specific FLPo system integrated into the pdx1 gene, allowing for targeted gene recombination in pancreatic cells.
  • This new method led to the development of pancreatic cancer in mice, mirroring traits seen in previous models, showcasing its potential for studying gene functions in pancreatic conditions.

Article Abstract

Background: Tissue and cell-specific gene targeting has been widely employed in biomedical research. In the pancreas, the commonly used Cre recombinase recognizes and recombines loxP sites. However, to selectively target different genes in distinct cells, a dual recombinase system is required.

Method: We developed an alternative recombination system mediated by FLPo, which recognizes frt DNA sequences for pancreatic dual recombinase-mediated genetic manipulation. An IRES-FLPo cassette was targeted between the translation stop code and 3-UTR of the mouse pdx1 gene in a Bacterial Artificial Chromosome using recombineering technology. Transgenic BAC-Pdx1-FLPo mice were developed by pronuclear injection.

Results: Highly efficient recombination activity was observed in the pancreas by crossing the founder mice with Flp reporter mice. When the BAC-Pdx1-FLPo mice were bred with conditional FSF-KRas and p53  mice, pancreatic cancer developed in the compound mice. The characteristics of pancreatic cancer resembled those derived from conditional LSL-KRas and p53  mice controlled by pdx1-Cre.

Conclusions: We have generated a new transgenic mouse line expressing FLPo, which enables highly efficient pancreatic-specific gene recombination. When combined with other available Cre lines, this system can be utilized to target different genes in distinct cells for pancreatic research.

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Source
http://dx.doi.org/10.1016/j.pan.2023.06.013DOI Listing

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