Generating Mouse Models of Degenerative Diseases Using Cre/Lox-Mediated In Vivo Mosaic Cell Ablation

The study developed mouse models using Cre/lox-mediated recombination to induce tissue-specific cell death, creating models for degenerative diseases. In Ins2-Cre;Mos-iCsp3 mice, pancreatic β cell ablation led to impaired glucose tolerance but not diabetes, with partial normoglycemia restoration due to β cell hyperplasia. In Krt14-CreER;Mos-iCsp3 mice, skin lesions were reversible, but focal alopecia persisted due to hair follicle stem cell depletion. In Pou4f3-Cre;Mos-iCsp3 mice, inner ear hair cell ablation caused permanent hearing loss, demonstrating the model's utility in studying cell-specific degeneration. The study showed that AP20187 administration led to significant hair cell ablation, with a 49.5% reduction in vitro and a 24.6% loss in vivo, resulting in moderate hearing impairment, confirming the model's potential for studying hair cell-specific deafness.