Accession Number:

ADA609750

Title:

Translational Research for Muscular Dystrophy

Descriptive Note:

Annual rept. 1 May 2013-30 Apr 2014

Corporate Author:

JACKSON LAB BAR HARBOR ME

Personal Author(s):

Report Date:

2014-05-01

Pagination or Media Count:

11.0

Abstract:

The overall goal of this work is to increase the availability of critical mouse models of human muscular dystrophy MD for both hypothesis testing and preclinical therapy development. Our multi-disciplinary team from The Jackson Laboratory JAX and the Children s National Medical Center CNMC has expertise in MD, repository management, mouse models, and preclinical testing. For Year 3 of funding, Drs. Lutz and Cox at JAX have added 7 new strains to the MD Repository Aim1 to leverage JAX s considerable expertise and infrastructure to maintain and distribute MD mouse resources to the scientific community. In Aim 2 we have completed gene targeting of dystrophin transgenes into DBA2J ES cell lines and are screening chimeric mice for germ-line transmission. These novel DMD transgenic mice, which model patients receiving successful exon-skipping therapies, will be crossed to mutant D2.B10-mdx to score for phenotypic rescue of each mutant and WT line to compare the functionality of resulting Dystrophin molecules containing in-frame deletions that are expected to arise by successful treatment of patient mutations. In Aim 3, we have completed generation of a DBA2J congenic mdx strain that appears to better model the symptoms of the human disease. In addition, we are screening F2 crosses between B6 and D2 to identify genetic modifiers that can alter disease onset and severity. In Aim 4, Dr. Nagaraju at CNMC has performed a baseline phenotypic analysis of our new D2.B10-mdx model and we are combining the analysis from JAX and CNMC to write a manuscript detailing the advantages of this new model for preclinical testing. A no-cost extension for a fourth year of work was awarded to allow completion of our transgenic analysis of Becker-like muscular dystrophy rescue experiments, allow completion of the D2.B10-mdx characterization and preclinical evaluation of this improved model. Our DMD repository has greatly expand the accessibility and availability of mouse model resourc

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE