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Mouse Genetic Models Core

Director

David Ornitz
Developmental Biology
314-362-3908
dornitz@wustl.edu

Associate Director

Fanxin Long
Orthopaedic Surgery
314-454-8795
longf@wudosis.wustl.edu

Mouse Model Database

Debabrata Patra
314-454-8823
patrad@wudosis.wustl.edu

Billing Administrator

Kami McGhee
Orthopaedic Surgery
314-747-5993
314-454-5900 - fax
mcgheek@wudosis.wustl.edu

Overview

Mouse genetic models have been extensively utilized by MRC investigators and are central to research in musculoskeletal biology and medicine. The Animal Models Core aims to facilitate the implementation of new technology, and the production, acquisition, and sharing of pertinent mouse genetic models among MRC investigators, as well as provide training and education for non-expert users. To foster a state-of-the-art research environment for MRC researchers, the Animal Models Core will work to support the optimization and implementation of new technologies, the generation of mouse genetic tools that will have wide use among MRC researchers, the production, preservation, and sharing of genetically altered mice in a timely and reliable manner, and the exploration of the zebrafish as a model for musculoskeletal research. Specifically, the Animal Models Core provides the following services:

1. Consultation and education on mouse genetic models.
We will advise and educate new and non-expert users on state-of-the-art and emerging technologies, mouse and zebrafish genetic strategies, target and transgene design, as well as colony management.

2. Production of novel genetic tools and models to support research on musculoskeletal diseases.
We will implement emerging technology, generate novel genetic tools to advance musculoskeletal research, and foster the development of investigator-initiated generation of novel mouse models.

A. We will develop TAL Effector Nuclease (TALEN) technology for gene targeting in mice and advance the technology to allow efficient re-engineering of established mouse knockin alleles.

B. We will help core investigators generate specific mouse models. The investigator will initiate a project by identifying the desired mouse models. For ES cell knockout studies, the investigator will either acquire targeted ES cells from the International Knockout Mouse Consortium (IKMC), or generate targeted ES cells with core guidance and technical support from the Transgenic Vector Core (TVC) and Murine Embryonic Stem Cell Core (ES Core). Alternatively, novel TALEN (and CRISPR/Cas) technology, can be implemented. For DNA injection, the investigator will provide the transgene or TALEN construct. Microinjections of either correctly targeted ES cells or DNA/RNA constructs will be performed at the Mouse Genetics Core (MGC).

3. Develop the use of zebrafish models in musculoskeletal research.
For many biological and medical questions, the zebrafish has become an optimal model of development and disease. The zebrafish offers many advantages for basic developmental and disease studies, including rapid external development of transparent embryos, susceptibility to mutagens, and the ability to knockdown endogenous gene expression and introduce transgenes into the germline. We will facilitate the use of TALEN and CRISPR technologies to modify the zebrafish genome. We will provide education and access to zebrafish technology and facilities.

4. Establish and maintain a campus-wide database for mouse and zebrafish strains.
We maintain and update a database of available transgenic mouse strains to facilitate reagent sharing within the musculoskeletal community. We will establish a zebrafish mutant database to facilitate the use of this model organism.

 

Figure 1. A flow chart for the production and utilization of mouse genetic models at the MRC Mouse Genetic Models Core. Procedures and advice provided by the Mouse Genetic Models Core are highlighted in green boxes. The knockout category includes conventional, tissue-specific (Cre-loxP or Flt-Frt mediated) knockout and knockin strategies, as well as the use of TALENs and CRISPR/Cas. The transgenics category includes expressing any exogenous coding sequences (e.g. GFP) from a DNA construct containing cis-acting regulatory sequences. Abbreviations: IKMC: International Knockout Mouse Consortium; CreERT2: tamoxifen (TM)-inducible Cre recombinase; rtTA: reverse tetracycline-controlled transcriptional activator; BAC: bacterial artificial chromosome; KO: knockout; Stem Cell Core: Washington University Siteman Cancer Center ES Core; MGC: Washington University Mouse Genetics Core; MRC: Musculoskeletal Research Center.

Download Core D Flow Chart


Transgenic and Recombinant Mouse Models (click to view presentation)


Citing the grant in publications:


“Washington University Musculoskeletal Research Center (NIH P30 AR057235)”