GEMMs

GEMMs, or genetically engineered mouse models, are mice engineered to carry defined genetic alterations that model human diseases or gene functions in vivo. They are used to study disease mechanisms, validate therapeutic targets, and test interventions in a whole-organism context, providing a closer approximation to human biology than many in vitro systems or non-engineered animals. GEMMs enable investigation of gene function across development, physiology, and aging within intact tissues and organ systems.

Common approaches include transgenic mice with random integration of a transgene, targeted knockouts that disrupt a gene, and knock-ins that insert specific mutations or reporter alleles. Conditional models use site-specific recombinases such as Cre-LoxP or Flp-FRT to achieve tissue- or time-specific gene modification, allowing circumventing embryonic lethality or studying gene roles in particular contexts. CRISPR/Cas9 genome editing has accelerated model generation by enabling direct editing in zygotes or cultured stem cells, reducing the time to obtain informative lines. GEMMs can be global or tissue-restricted, and may be time-controlled to study aspects of disease progression.

Applications span cancer, neurodegenerative and metabolic diseases, immunology, and developmental biology. Notable examples include KRAS-driven pancreatic cancer models, and APP/PS1 or tau models used to study Alzheimer's disease. Strengths of GEMMs include physiological gene regulation, intact tissue interactions, and relevance to developmental processes. Limitations include long generation times, cost, the influence of genetic background, and occasional failure to fully recapitulate human pathology due to species differences. Ethical considerations and rigorous phenotyping, genotyping, and reporting are essential in GEMM research.