Special Mouse Strain Resource

Grant Number: P40OD011102

Research Emphasis/Objectives

Many aspects of human health and disease are genetically complex; that is, they arise from multiple interactions between genetic, developmental, and environmental factors. Understanding this complexity is the basis of personalized medicine. Unfortunately, human genetic studies are still limited in a number of ways. These include inadequate, retrospective medical records; formidable sample size requirements; insufficient statistical power to study genetic interactions; and insufficient mechanistic information about many genes. These obstacles are easily addressed using nonhuman mammalian models, such as mice, that are designed for fine-scale dissection of genetic complexity (i.e., systems genetics). For these reasons, the biomedical research community has invested in the development genetically diverse inbred strains and genetic reference populations of mice as tools for systems genetics research.

The Special Mouse Strain Resource (SMSR) at The Jackson Laboratory serves as the biorepository for these unique sets of strains, ensuring permanent and open access from high health status, quality controlled, state-of-the-art facilities. The resource currently consists of more than 300 strains, including the widely used BXD and Collaborative Cross strain panels, but importantly, the strains available in the SMSR are changed and developed as dictated by the needs of research community.

The major activities of the SMSR are to (1) archive, maintain, and distribute these strains to qualified biomedical researchers, (2) provide complete, accurate, and accessible information related to the mouse resources, (3) confer with an external advisory board of thought leaders from the complex trait community to define current and future resources, and (4) provide leadership in best practices for research and reproducibility using SMSR resources.

The SMSR also provides infrastructure, outreach, and collaborative opportunities for the development of new tools for complex trait analysis, as well as access to existing strains and populations for large-scale multicenter projects. It also conducts research to expand tools for genetic engineering of specialized mapping strains.

Current Research

The CC/DO and BXD platforms harness the natural inbred strain variation that is needed for systems genetics studies. The nine-founder inbred strains (A/J, 129S1/SvImJ, NZO/HILtJ, NOD/LtJ, CAST/EiJ, WSB/EiJ, PWK/EiJ, C57BL/6J, and DBA/2J [BXD]) from which this natural variation is derived are often used at the outset of a systems genetics study to establish heritability, a process that requires a survey of inter- to intrastrain variance in quantitative phenotypic trait(s). These genetically diverse inbred strains are also frequently used for validation studies of variants that underlie QTL. In both types of studies, genetic engineering is often required to achieve the goals of a given experiment. These manipulations include introduction of disease driver alleles, cell/tissue-specific fluorescent reporters, epitope-tagged proteins, conditional alleles, and other engineered molecular "tools," as well as simple allele swaps. Unfortunately, "tool strains" that carry commonly needed genetic manipulations are not currently available for genetically diverse inbred strains such as CC/DO, BXD, or the founder inbred strains used to create these RI panels. To address this gap, the SMSR program will create a series of commonly used tool strains across genetically diverse backgrounds.

Services Provided

The SMSR offers the following services in concert with The Jackson Laboratory: (1) breeding and rederivation services, including dedicated supply, speed expansion, congenic development, strain rescue, and microinjection; (2) cryopreservation, storage, and recovery services, including sperm and embryo cryopreservation; (3) phenotyping and pathology services; and (4) genome sciences services, including gene mapping, genome scanning, and QTL analysis.

Contact Information

JAX SMSR
The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609
Special Mouse Strain Resource

Principal Investigators

Laura Reinholdt, Ph.D.
Phone: 207-288-6693
laura.reinholdt@jax.org

Cat Lutz, Ph.D.
Phone: 207-288-6341
cat.lutz@jax.org