Why Are 129 Mice So Common in Scientific Research?

The 129 mouse is an inbred strain frequently used in biomedical research. Its prevalence is the result of a combination of historical development, unique genetic traits, and its foundational role in creating genetically modified organisms. This specific mouse strain offers insight into how laboratory models are developed to study a wide range of biological processes and human diseases. These mice are particularly notable in genetics, immunology, and cancer studies.

Origin and Development of 129 Mice

The 129 mouse strain’s lineage can be traced to a cross made by C.C. Little in 1920. The resulting offspring were maintained through careful inbreeding. This process of brother-sister mating for many generations creates a population of mice that are nearly genetically identical, a feature that reduces genetic variability in scientific experiments.

A significant development occurred with the work of Dr. Leroy Stevens at The Jackson Laboratory in the 1950s. Stevens was studying a high incidence of spontaneous testicular teratomas, a type of germ cell tumor, in a specific 129 substrain. His investigation into these tumors led to the derivation of embryonic carcinoma cells, which were the precursors to embryonic stem (ES) cells.

The ability to derive stable ES cell lines from 129 mice was a turning point, as these pluripotent cells became the primary vehicle for creating knockout mice through gene targeting. This history established the 129 mouse as a foundational tool in modern molecular genetics.

Key Genetic and Phenotypic Traits

One of the most significant traits is the high rate of spontaneous testicular teratomas in certain substrains. This predisposition to tumor formation makes the strain a useful model for studying germ cell development and cancer.

From a genetic standpoint, the 129 genome has a unique “plasticity.” This refers to the fact that ES cells derived from 129 mice were the most reliable for genetic manipulation and for creating viable chimeric mice. Even when crossed with other strains, the 129 genetic background often enabled success. The specific factors contributing to this genomic plasticity are still being investigated.

Phenotypically, 129 mice have a docile temperament, which makes them easier to handle in a laboratory setting. Behaviorally, they can show differences in learning and memory tasks and are sometimes used in studies of anxiety and depression. However, they are also known for having relatively poor breeding performance, which can present logistical considerations for researchers.

Prominent Research Uses

The most prominent role for 129 mice has been in genetics, specifically for the creation of knockout mice. This strain became the default for countless experiments aimed at understanding the function of a specific gene by “knocking it out” or rendering it inactive.

This application in genetics extends directly to developmental biology. By creating mice with targeted mutations, researchers can study how specific genes influence embryonic development, organ formation, and cellular differentiation. The use of 129-derived ES cells has been instrumental in understanding the genetic pathways that guide an organism’s growth.

Beyond gene targeting, the 129 strain is used in cancer research, a legacy of Dr. Stevens’ early work on teratomas. Its predisposition to certain types of tumors makes it a valuable model for investigating cancer initiation, progression, and potential therapies. The strain is also utilized in immunology and in studies related to metabolic diseases like diabetes and obesity.

Understanding 129 Substrains

The “129 mouse” is not a single, uniform entity. In reality, the 129 strain is a collection of numerous distinct substrains, each with its own genetic identity and history. These substrains arose over decades as different laboratory populations were bred in isolation, leading to genetic drift and the accumulation of spontaneous mutations. This resulted in significant genetic and phenotypic differences between them.

The nomenclature of these substrains, such as 129S1/SvImJ or 129P3/J, provides information about their lineage and the laboratory where they were maintained. The main divisions are the “Parental” (P), “Steel” (S), and “Teratoma” (T) lineages. For instance, the 129S1/SvImJ substrain was developed to serve as a control for ES cell lines derived from the “Steel” lineage, which carries a specific mutation affecting coat color and other systems.

These differences can have profound impacts on research outcomes. For example, the incidence of testicular teratomas can vary from 1-3% in some substrains to as high as 30% in others. This variability means that researchers must be precise in selecting and reporting the specific 129 substrain used. Matching the genetic background of the ES cell line to the correct substrain is necessary for accurate gene-targeting experiments, ensuring results are reproducible and correctly interpreted.