Somatic Genome-Engineered Mouse Models Using In Vivo Microinjection and Electroporation.

Area of Science:

• Genetics
• Cancer Biology
• Mouse Models

Background:

• Germline genetically engineered mouse models (G-GEMMs) are valuable but costly and time-consuming.
• Somatic genetically engineered mouse models (S-GEMMs) offer an alternative by directly targeting specific tissues.
• High-grade serous ovarian carcinomas (HGSCs) originate in specific regions of the human oviduct, unlike traditional mouse models.

Purpose of the Study:

• To develop a novel, cost-effective method for generating S-GEMMs that accurately models human ovarian cancer initiation.
• To target specific regions of the oviduct, mimicking the human disease origin.
• To overcome the limitations of traditional G-GEMMs and whole-oviduct targeting models.

Main Methods:

• Microinjection of DNA, RNA, or ribonucleoprotein (RNP) solutions into the oviduct lumen.
• In vivo electroporation to target mucosal epithelial cells in restricted oviduct regions.
• Utilized CRISPR-mediated genome editing for precise genetic modifications.

Main Results:

• The method allows adaptable targeting of specific oviduct regions and cell types.
• It offers flexibility in the number of edited cells and gene mutation combinations.
• The approach enables immunocompetent disease modeling without requiring specific mouse lines and allows for cell tracking.

Conclusions:

• This novel method provides a cost-effective and adaptable approach to generate S-GEMMs for studying HGSC initiation.
• It accurately recapitulates human ovarian cancer initiation in specific oviduct regions.
• The technique enhances the utility of mouse models for cancer research and drug development.