Generating somatic mosaicism with a Cre recombinase-microsatellite sequence transgene

Area of Science:

• Genetics and Genomics
• Molecular Biology
• Mouse Models in Research

Background:

• Generating mosaic genotypes in mouse tissues is challenging.
• Existing methods for altering mouse genotypes are limited in generating tissue-specific mosaics.

Purpose of the Study:

• To develop a novel approach for generating mosaic genotypes in mouse tissues.
• To demonstrate the utility of this method for studying gene function and disease.

Main Methods:

• Utilized a modified Cre recombinase transgene with a reading frame-altering mononucleotide tract.
• Achieved stochastic activation of the Cre transgene in the mouse intestinal tract.
• Induced colonic polyposis via Cre-mediated bi-allelic inactivation of the Apc gene.

Main Results:

• Successfully generated mosaic genotypes in the mouse intestinal tract.
• Demonstrated stochastic activation of the Cre recombinase.
• Successfully induced colonic polyposis, validating the approach for disease modeling.

Conclusions:

• The developed method provides a powerful tool for generating mosaic genotypes in mice.
• This technique facilitates the study of gene function in specific cell populations within tissues.
• The approach is useful for modeling diseases like colonic polyposis.