Mice (Laboratory) - Pathology

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Genetically Engineered Mice

Terminology

Definitions: Genetically engineered mice have induced mutations, including transgenes, targeted mutations (knockouts or knockins), and retroviral, proviral, or chemically-induced mutations.

Transgenic mice carry a segment of foreign DNA incorporated into their genome via non-homologous recombination (e.g., pronuclear microinjection), infection with a retroviral vector, or homologous insertion.

Targeted mutant mice are produced by first inducing gene disruptions, replacements, or duplications into embryonic stem (ES) cells via homologous recombination between the exogenous (targeting) DNA and the endogenous (target) gene. The genetically-modified ES cells are then microinjected into host embryos at the eight-cell blastocyst stage. These embryos are transferred to pseudopregnant host females, which then bear chimeric progeny. The chimeric progeny carrying the targeted mutation in their germ line are then bred to establish a line. If the newly established line has a disrupted or deleted gene, it is called a knockout; if it has a new or duplicated gene, it is called a knockin.

Mice with chemically-induced mutations are produced by using a variety of chemicals. One popular chemical mutagen, ethylnitrosourea (ENU), is used to induce point mutations. ENU mutagenesis involves exposing male mice to ENU and then mating the treated males to untreated females. The resultant progeny, many of which carry point mutations, are screened for phenotypes of interest.

Applications

Genetically engineered mice are useful for elucidating basic biological processes, studying relationships between gene mutations and disease phenotypes, and modeling human disease. Research applications are included on strain data sheets in the JAX® Mice Database. The applications are compiled using a number of information sources (please refer to Mouse Information Resources), but they are not all-inclusive: rapidly advancing biomedical research continually uncovers new applications and uses for genetically engineered and mutant mice strains.

Some genetically engineered and mutant mice strains have a mutation associated with a specific human disease. If the gene or mutation is orthologous to that in humans and causes the same disease in humans, the strain is designated as a model of the human disease. Manifestation of the genetic mutation (phenotypic expression) may differ between humans and mice. Investigators are strongly encouraged to research recommended mouse models to be sure they are appropriate for their research.

http://jaxmice.jax.org/type/gemm/index.html