Associate Professor
Office: Wegner Hall 111
Email:
lsprunger@vetmed.wsu.edu
Telephone: (509) 335-7071
Fax: (509) 335-4650
The combination of classical and molecular genetics with physiology is a
powerful means of identifying and studying biological processes. I am
interested in integrating physiological methods with the the tools of
molecular genetics to study the role of voltage-gated Na+ channels in
the nervous system in general and in control of movement and movement
disorders in particular.
Scn8a is a neuronal Na+ channel that contributes to the classical
transient Na+ current during an action potential, and in some neurons
also mediates distinct subthreshold currents that affect firing patterns
and excitability. Different mutations in Scn8a cause a spectrum of
neurologic dysfunction, including tremor, ataxia, dystonia, paresis, and
paralysis. However, because the gene is expressed in so many places in
the central, peripheral, and enteric nervous systems, the resulting
phenotypes are difficult to study due to their complexity. We have used
the approach of generating conditional or targeted mutations in
restricted cell types in mice to better understand the role of this gene
in specific neural pathways.
Recent work in my lab (and in conjunction with collaborators) includes
three major projects. One line of investigation has been to elucidate
the spatial distribution of Scn8a and other related sodium channel genes
in the enteric nervous system with the objective of better understanding
the determinants of neuronal excitability in the gut. A second project
has been directed at understanding a possible novel and unexpected role
of this gene in the heart. Most recently, we have developed a novel
mouse model of dystonia using the targeted gene inactivation approach.
Dystonia is a movement disorder typified by sustained abnormal postures
and twisting movements. The anatomic origin(s) and pathophysiology of
dystonia are poorly understood. Secondary dystonias have been associated
with lesions of the basal ganglia, but clinical or experimental evidence
for a similar origin of primary dystonias is lacking. Scn8a mutant mice
constitute the first association of an ion channelopathy with dystonia.
These mice should help to clarify the role of Scn8a in specific regions
of the brain and spinal cord, and their respective contributions to
dystonia.
Biographical Information
Leslie Sprunger received a B.S. in Biological Science from the
University of Alaska, Fairbanks (1983), a D.V.M. from Washington State
University (1987), and entered private practice as a small animal
veterinarian. Dr. Sprunger returned to academia to earn a Ph.D. in
Physiology (1995) from the University of Minnesota Department of
Veterinary Pathobiology, where she was the recipient of a Graduate
School Fellowship, the Louise T. Dosdall Fellowship for Women in
Science, the Charles and Dorothy Andrew Bird Award for Research, and a
Howard Hughes Medical Institute predoctoral fellowship. An NIH Clinical
Investigator Development Award funded Dr. Sprungers post-doctoral
training in the University of Minnesota Medical School Department of
Physiology, and the Department of Human Genetics at the University of
Michigan Medical School. Dr. Sprunger was appointed research faculty at
University of Michigan in 1999, and joined the Department of VCAPP as
Assistant Professor in July 2000.
Selected Publications
Raman, I.M.,
L.K. Sprunger, M.H. Meisler, and B.P. Bean. (1997) Altered
subthreshold sodium currents and disrupted firing patterns in Purkinje
neurons of Scn8a mutant mice. Neuron, 19:881-891.
Garcia, K.,
L.K. Sprunger, M.H. Meisler, and K. Beam. (1998) Postnatal
development of sodium current density in normal and med motoneurons. J.
Neurosci., 18:5234-5239.
Sprunger, L.K., A. Escayg, S. Tallaksen-Greene, R.L. Albin, and M.H.
Meisler. (1999) Generalized dystonia associated with mutation of the
neuronal sodium channel Scn8a: role of the modifier locus Scnm1 on mouse
chromosome 3. Hum. Mol. Genet. 8:471-479.
Buchner, D.A., M. Trudeau, A.L. George,
L.K. Sprunger, and M.H. Meisler.
(2003) High resolution mapping of the sodium channel modifier
Scnm1 on mouse chromosome 3 and identification of a 1.3 kb recombination
hotspot. Genomics 82(4): 452-459.
Meisler, M.H., N.W. Plummer, D.L. Burgess, D.A. Buchner, and L.K.
Sprunger. (2004) Allelic mutations of the sodium channel
SCN8A reveal multiple cellular and physiological functions.
Genetica (Netherlands) 122: 37-45.
Sprunger, L.K., and T.L. Smith. (2005) Reorganizing small
animal gross anatomy: improving the faculty and student experience and
incorporating non-technical competency development. J. Vet. Med.
Educ. 32: 255-263.
Bartoo, A.C.,
L.K. Sprunger, and D.A. Schneider. (2005)
Expression and distribution of TTX-sensitive sodium channel alpha
subunits in the enteric nervous system. J. Comp. Neurol. 406:
117-131.
Bartoo, A.C.,
L.K. Sprunger, and D.A. Schneider. (2006)
Expression of the sodium channel Nav1.2 in chemically identified
myenteric neurons in the guinea pig. Cell Tiss. Res. 324(1):
25-32.
PubMed Publications (Note: PubMed Search may produce additional
"Springer" authors.)
