What are transgenic mice? - briefly
Transgenic mice are laboratory rodents engineered to incorporate foreign DNA into their genome, enabling the expression of introduced genes. They serve as models for human diseases, tools for functional genomics, and platforms for therapeutic testing.
What are transgenic mice? - in detail
Transgenic mice are laboratory rodents whose genome has been altered to carry one or more foreign genes introduced through recombinant DNA techniques. The inserted DNA integrates into the host chromosome, resulting in stable inheritance of the new trait in subsequent generations.
The creation process typically follows these steps:
- Isolation of a DNA fragment containing the gene of interest and regulatory elements.
- Construction of a vector, often a plasmid or bacterial artificial chromosome, to carry the fragment.
- Introduction of the vector into fertilized mouse eggs by microinjection, electroporation, or viral transduction.
- Implantation of the modified embryos into surrogate females.
- Screening of offspring for the presence and expression of the transgene using PCR, Southern blotting, or reporter assays.
Applications span multiple fields:
- Disease modeling: mice engineered to express human disease genes reproduce pathological features of conditions such as Alzheimer’s, cancer, and diabetes, enabling mechanistic studies and drug testing.
- Gene function analysis: loss‑of‑function or gain‑of‑function mutations reveal the role of specific proteins in development, physiology, and behavior.
- Biotechnology production: transgenic lines serve as bioreactors for therapeutic proteins, antibodies, and enzymes.
- Immunology: expression of human immune components facilitates the evaluation of vaccines and immunotherapies.
Advantages include precise genetic control, rapid breeding cycles, and the ability to produce large, homogeneous cohorts. Limitations involve potential insertional mutagenesis, variable expression due to positional effects, and differences between murine and human biology that may affect translational relevance.
Ethical considerations require compliance with institutional animal care guidelines, justification of experimental necessity, and implementation of the 3Rs principle—replacement, reduction, and refinement—to minimize animal use and suffering.
Notable examples:
- APP/PS1 mice expressing mutant amyloid precursor protein and presenilin‑1, used extensively in Alzheimer’s research.
- Lep^ob/ob mice carrying a mutated leptin gene, serving as a model for obesity and metabolic syndrome.
- Humanized immune system mice engrafted with human hematopoietic stem cells, valuable for studying HIV infection and immunotherapies.