Mark A. Erhart, Ph.D.
Department of Biological Sciences
We have identified a phenotypic deviant within our CSU mouse colony that shows an
adult-onset, progressive ataxia. Breeding analysis of this deviant strain (BxR23)
suggests that the underlying cause of this ataxia is a Mendelian trait, transmitted
in an autosomal dominant manner. Differences in severity of the phenotype between
homozygotes and heterozygotes, however, suggest that the trait is incompletely dominant.
We hypothesize that the mutation responsible for this trait resides in an as yet uncharacterized
mouse gene. An alternative hypothesis is that the mutation resides in a mouse gene
that has been previously characterized. We are attempting to distinguish these alternatives
by simultaneously mapping the mutation within the mouse genome through linkage analysis
and developing mutation-detection assays for several candidate mouse genes. Necropsies
of affected BxR23 mice have failed to identify a clear physiological basis for the
ataxic phenotype, so a genetic approach is clearly the best way to characterize this
disorder. We are also currently documenting the onset and progression of the ataxia
through standard observation methods such as balance beam tests and stride length
measurements. In this way, a quantitative measure of phenotypic difference between
homozygotes and heterozygotes can be attained. Although there are dozens of human
ataxia syndromes caused by autosomal dominant mutations, there are no known mouse
models of dominant ataxias. The BxR23 mouse may prove to be a useful model for studying
the development of adult-onset, progressive ataxias in humans.
Neurodegenerative diseases exact an enormous toll on the aging human population. Many
of these diseases are inherited in an autosomal dominant fashion. Mouse models for
these diseases, like the BxR23 mouse strain, are valuable tools in understanding the
molecular and biochemical basis of human neurodegenerative disorders.
Wallace LT and Erhart MA (2008). Recombination within mouse t haplotypes has replaced significant segments
of t-specific DNA. Mammalian Genome 19 (4):263-271.
Erhart MA, Kim T, Crews GM, Pandya A (2006). The use of unilateral PCR to resolve prominent
heteroduplexes formed during PCR of the mouse microsatellite locus D17Mit23. Molecular
Biotechnology 33, 37-48.
Osei-Bonsu D* and Erhart MA (2005). An integrative physiology investigation of an autosomal dominant
neuromuscular disorder in a recombinant inbred mouse. Sixteenth Annual Student Research
Conference, Oak Brook, IL, April 24, 2005.
* RISE student presenter
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