Transgenic mouse models are genetically engineered mice in which specific genes have been inserted, modified, or removed to study gene function, disease mechanisms, or develop and test potential therapies. These models are valuable tools in biomedical research because mice share a high degree of genetic similarity with humans, have relatively short generation times, and are easy to breed and maintain in laboratory settings.

Transgenic mouse models are created using several genetic engineering techniques:

1. Pronuclear microinjection: This technique involves injecting a DNA construct containing the desired gene or modification into the pronucleus of a fertilized mouse egg. The injected DNA integrates into the mouse genome, and the fertilized egg is then implanted into a surrogate mother. The resulting offspring carry the transgene and can be used to establish a transgenic mouse line.
2. Embryonic stem (ES) cell-mediated gene targeting: This method allows for more precise manipulation of the mouse genome by introducing the desired genetic modification into mouse embryonic stem cells using homologous recombination. The modified stem cells are then injected into mouse blastocysts, which are implanted into a surrogate mother. The offspring that carry the modified ES cells in their tissues can be bred to establish a transgenic mouse line.
3. CRISPR/Cas9 genome editing: CRISPR/Cas9 is a powerful gene-editing tool that enables targeted modifications of the mouse genome with high precision and efficiency. By introducing the Cas9 enzyme and a guide RNA targeting the desired genomic location into mouse embryos, researchers can create specific mutations, insertions, or deletions in the mouse genome. The edited embryos are then implanted into a surrogate mother to generate transgenic mice.

Transgenic mouse models can be designed for various research purposes:

1. Gene function studies: By overexpressing or deleting specific genes in mice, researchers can gain insights into their roles in development, physiology, and disease.
2. Disease models: Transgenic mice can be engineered to carry human disease-associated genes or mutations, allowing researchers to study disease mechanisms, identify potential drug targets, and test new therapies in a more relevant context.
3. Reporter gene expression: Mice can be engineered to express reporter genes, such as those encoding fluorescent proteins or enzymes, under the control of specific promoters or regulatory elements. This enables researchers to visualize gene expression patterns or monitor cellular processes in living mice.
4. Conditional gene manipulation: Transgenic mice can be designed with “floxed” genes that can be specifically deleted or activated in certain tissues or at specific developmental stages, providing researchers with temporal and spatial control over gene expression.

Transgenic mouse models have contributed significantly to our understanding of gene function, disease mechanisms, and the development of new therapies. However, it is essential to recognize that findings from these models may not always directly translate to humans, and complementary research approaches are often necessary to validate and expand upon discoveries made in mice.