Pediatric Disease Mouse Models Core

PDMMC

PEDIATRIC DISEASE MOUSE MODELS CORE (PDMMC)

Precisely altering the mouse genome is a key approach used in biomedical research to model human disease.  Mutant mice have contributed to understanding and treating human disorders, including childhood brain and other cancers, muscular dystrophies, diabetes, congenital heart and lung diseases, and other types of birth defects.  Difficulties and risks in making mutant mice include the requirement for specialized expertise and significant time and cost.

The major goal of the Pediatric Disease Mouse Models Core is to generate mouse models of pediatric disease using state-of-the-art CRISPR/Cas9 and ROSA-TALEN technologies, which significantly decrease the associated time and costs.  The Core’s services will support the CDI’s goal of expediting mutant mouse production for precision genomic approaches in pediatric disease research.  This will benefit the many CDI members, both currently CDI-funded and not, who use or wish to use mouse models to study pediatric disease.

SERVICES TO BE PROVIDED BY THE CORE

The Pediatric Disease Mouse Models Core (PDMMC) will provide a complete, well-established mouse production pipeline and premium support services. This highly integrated service will significantly reduce CDI investigator costs because all stages of the pipeline, from initial consultation and project design through microinjections/electroporations and initial genotyping, will be eligible for subsidy of 70% of the total costs through a micro-grant application process.  The CDI Award will support the following services:

  1. Consultation for project strategy
  2. Coordinated project management of complex services from project start to finish
  3. Design and generation of CRISPR/Cas9 and ROSA-TALEN reagents
  4. Delivery of reagents to embryos by microinjection or electroporation
  5. Initial genotyping of potential founder mice
  6. Custom genotyping design and consultation
  7. Breeding consultation
  8. Significant offset of charges related to all services needed for model creation

The specific types of gene-edited mice to be produced include the following:

  • Insertion of point mutations at endogenous loci
  • Constitutive gene knockouts
  • Conditional knockouts and knock-ins
  • ROSA26 locus constitutive and conditional knock-ins using a transcription activator-like effector nuclease (TALEN) approach
  • Reporter and other cassette knock-ins
OPERATION OF THE CORE

The PDMMC will carry out its mission by subsidizing the usage of existing institutional cores with outstanding track records.  These include:

Dr. Jeff Miner (jeffminer@wustl.edu) will serve as the primary contact for CDI investigators and center members wishing to access services.  Potential users will submit to Dr. Miner a one page "micro-grant" providing information about:

  1. the PI (including all contact information)
  2. whether the PI is a CDI member
  3. whether the PI has CDI funding
  4. the scientific background and major hypothesis of the project
  5. the project's relevance to the goals of the CDI
  6. the general nature of the mouse mutant to be made
  7. the plan for characterizing the mouse and using it to test the overall hypothesis

There will not be specific micro-grant deadlines; micro-grants will be accepted on a rolling basis and evaluated to determine if project is appropriate for CDI subsidy in order to ensure that the Core supports the best science that is also relevant t the goals of the CDI.

50% of the funding will be reserved for subsidies for projects that involve cancer. In addition, 33% of funds for subsidies will be reserved for faculty who hold a research grant from the CDI. There will likely be some overlap between these two groups.  Other funds will be used to subsidize meritorious CDI member projects that are clearly relevant to the overall goals of the CDI.  The amount of subsidy available to individual PIs will depend on the overall demand for Core services, but the projected limit is a subsidy of $7,000 per year per PI.

COSTS FOR CORE SERVICES:

The cost for generating a new mouse model will vary substantially, depending on the complexity of the required gene editing.  The PDMMC’s goal is to cover 70% of the total costs, which is a substantial discount that will not encourage misuse of the Core’s resources. Limiting the subsidy to 70% also allows more projects to be subsidized.  Core users will be able to choose whether to have the Transgenic Vectors Core or the GEiC design and provide the CRISPR/Cas9 reagents to the Mouse Genetics Core for microinjection or electroporation into embryos.

ELIGIBILITY

Micro-grants are available for current CDI Investigators* and CDI center members** to support 70% of the cost of generating the new mouse model.

*CDI-funded postdoctoral fellows and PI’s of Educational Initiatives are not eligible to apply as a CDI Investigator for a micro-grant.

** A faculty appointment at the Instructor or Assistant Professor level and above is required to apply for a micro-grant as a CDI center member.  Please register here to become a CDI center member.

TERMS

Grantees are expected to cite CDI support for all publications, press releases or presentations citing results from this micro-grant and must include the following acknowledgement:  "Funding for this project was in part provided by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital."  A final report will be required at the end of the grant period.

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