A High-Throughput Transgenic Mouse Production System

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): While targeted gene ablation methods have
matured to the point that investigators can confidently design experiments that
will totally eliminate production of any protein, over-expression and ectopic
expression methods has not significantly evolved since the production of the
first transgenic mice in the late 1970s by DNA microinjection in fertilized
mouse oocytes. Because expression after random integration of multiple copies
of the transgene in the mouse genome is often unpredictable, this simple
microinjection method has become inadequate for many purposes. We propose here
to develop a system for high-throughput transgenic mouse production that will
generate animals that express transgene in a ubiquitous, tissue-specific or
inducible manner at predictable levels because the transgenes will be inserted
as single-copies at defined sites in the mouse genome. This new system will be
based on methods to perform site-specific chromosomal integrations using
Recombinase-Mediated Cassette Exchange directly in fertilized mouse oocytes, on
the development of standardized integration sites, and on the construction of
RMCE-enabled indexed cDNA libraries. Once frilly implemented, this new system
will enable investigators to study the function of any known mouse or human
cDNA by expressing ectopically, or at precisely defined graded levels of
over-expression with minimal efforts and at minimal costs.
StatusFinished
Effective start/end date9/30/018/31/02

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $167,417.00

ASJC

  • Genetics
  • Molecular Medicine
  • Molecular Biology
  • Biotechnology
  • Developmental Biology

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