Currently available or expected date of availability
Currently available (see below)
Requirements for use (by collaboration or fee-for-service, application
required, etc.)
We are open to a range of collaborations that could extend from
providing tissue samples to clinical trials. Funded studies have the
highest priority.
Brief description of services or resources (a paragraph or two)
Identification of dystrophin as the defective protein in Duchenne
muscular dystrophy (DMD) has allowed critical assessment of potential
animal models. Spontaneous forms of X-linked muscular dystrophy due to
dystrophin deficiency have been identified in mice, multiple dog breeds,
and cats. Over the past 20 years, w e have conducted extensive studies
in golden retrievers with muscular dystrophy (GRMD). Our colony of
affected dogs was initially established at North Carolina State
University in the late '80's and was moved to the University of Missouri
in 1994. Additional studies have been completed in German shorthair
pointers, Welsh corgis, and Yorkshire terriers.
An RNA processing error in GRMD results from a single base change in
the 3' consensus splice site of intron 6 (Sharp et al, 1991). Exon 7 is
consequently skipped during RNA processing. The resulting transcript
predicts that the dystrophin reading frame is terminated within its
N-terminal domain in exon 8. A truncated, apparently unstable dystrophin
molecule is produced. German Shorthaired pointers have a large DNA
deletion, essentially amounting to a dystrophin "knock out (Schatzberg
et al, 1999). We have both golden retrievers and German Shorthaired
pointers available for studies. The genomic lesion has not been defined
in Welsh Corgis or Yorkshire terriers.
So as to better utilize the GRMD model in therapeutic trials, we have
developed various phenotypic tests to objectively characterize disease
progression. Affected dogs have marked joint contractures (Kornegay et
al, 1994a) and demonstrate weakness of individual (Kornegay et al,
1994b) and grouped muscles (Kornegay et al, 1999). Results from these
tests tend to correlate with one another and with other
clinicopathologic features. Importantly, by comparing serial
measurements from treated and untreated groups, one can document
improvement or delayed progression of disease.