This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The sense of balance is an important way in which we perceive and interact with our environment. The sense of balance and spatial orientation is conveyed by sensory neurons in the semi-circular canals to the brainstem via the vestibulocochlear nerve. The information is then relayed to the Purkinje cells of the cerebellum, which are responsible for the fine control of movement. Degenerative disorders can irreversibly cause the loss of neurons along this pathway. There are currently no effective treatments to prevent or slow the death of neurons. The etiology of this broad group of disorders includes environmental and genetic insults and can occur late in life or during development. While powerful genetic studies have associated mutant alleles with disease phenotypes, the molecular cues that directly initiate neuron death remain uncertain. It is essential to address this knowledge gap so that neuroprotective strategies can be logically defined and rigorously tested in an in vivo model system. We have identified a vestibular disorder in the weeble mutant mouse (wbl) associated with a mutation in inositol polyphosphate 4-phosphatase (Inpp4a). This unique mouse model has common vestibular signs and an early-onset, patterned Purkinje cell degeneration during development. This patterned nature has facilitated our discovery of a candidate neuroprotective modifier gene that we propose to test for its ability to prevent the death of neurons. The long-term goal of our research is to identify the molecular and genetic mechanisms involved in the pathogenesis of degenerative movement and balance disorders in order that improved treatment strategies can be developed.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018788-08
Application #
8360399
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
8
Fiscal Year
2011
Total Cost
$198,548
Indirect Cost
Name
University of Nebraska Medical Center
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Amaradasa, Bimal S; Amundsen, Keenan (2016) Transcriptome Profiling of Buffalograss Challenged with the Leaf Spot Pathogen Curvularia inaequalis. Front Plant Sci 7:715
Gurumurthy, Channabasavaiah B; Grati, M'hamed; Ohtsuka, Masato et al. (2016) CRISPR: a versatile tool for both forward and reverse genetics research. Hum Genet 135:971-6
Connor, Alicia L; Kelley, Philip M; Tempero, Richard M (2016) Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis. Lab Invest 96:270-82
Küçük, Can; Hu, Xiaozhou; Gong, Qiang et al. (2016) Diagnostic and Biological Significance of KIR Expression Profile Determined by RNA-Seq in Natural Killer/T-Cell Lymphoma. Am J Pathol 186:1435-41
Connor, Alicia L; Kelley, Philip M; Tempero, Richard M (2016) Invariant asymmetry renews the lymphatic vasculature during homeostasis. J Transl Med 14:209
Küçük, Can; Hu, Xiaozhou; Jiang, Bei et al. (2015) Global promoter methylation analysis reveals novel candidate tumor suppressor genes in natural killer cell lymphoma. Clin Cancer Res 21:1699-711
Yuan, Yang; Seong, Eunju; Yuan, Li et al. (2015) Differential regulation of apical-basolateral dendrite outgrowth by activity in hippocampal neurons. Front Cell Neurosci 9:314
Reiner, Benjamin C; Dunaevsky, Anna (2015) Deficit in motor training-induced clustering, but not stabilization, of new dendritic spines in FMR1 knock-out mice. PLoS One 10:e0126572
Lundberg, Yunxia Wang; Xu, Yinfang; Thiessen, Kevin D et al. (2015) Mechanisms of otoconia and otolith development. Dev Dyn 244:239-53
Palmer, Nathan A; Donze-Reiner, Teresa; Horvath, David et al. (2015) Switchgrass (Panicum virgatum L) flag leaf transcriptomes reveal molecular signatures of leaf development, senescence, and mineral dynamics. Funct Integr Genomics 15:1-16

Showing the most recent 10 out of 83 publications