1. Versican Plays an Important Role in
Neural Development and Damage
Repair in the Cochlea
Meredith Hammer
The Governor’s School for Science and Mathematics
Mentor: Dr. Hainan Lang
Department of Pathology and Laboratory Medicine
The Medical University of South Carolina
4. Hearing Loss in Cochlea
Sensory –occurs when the hair cells in the cochlea are damaged
Neural – damage or degeneration in neurons of the auditory nerve
http://thehearingfix.com/types-of-hearing-loss/sensorineural-hearing-loss/
The Cochlea
The Organ Corti
5. Myelination and Nodes of Ranvier
http://bio1152.nicerweb.com/Locked/media/ch48/myelin.html
8. Versican (VCAN): Proteoglycan of the
Extracellular Matrix
• Proteoglycan: a protein/carbohydrate molecule
• VCAN is located around myelinated axons, specifically the Nodes of Ranvier
http://www.seehint.com/hint.asp?md=144&no=12735
9. Our Research
• We are interested in Versican because…
– Stress induced heart problems in VCAN V0/V2 knockout mice
– VCAN has not been studied in the cochlea
– VCAN accumulating in cochlea during postnatal development and injury
– VCAN KO and WT mice with similar hearing function before noise damage
• We are investigating its significance in the cochlea
by…
– Determining morphological differences between Versican V0/V2 knockout and
wild type mice
– Investigating the response of V0/V2 knockout mice to noise damage, in
comparison to wild type
10. Versican V0/V2 knockout mice
• Knockout mice compared with wild type
mice to investigate importance of
Versican in function and morphology
• Its V2 isoform has been studied
previously in the central nervous system
(Zimmermann, et. al.)
Affected ECM organization and
structure
Absence of Phosphocan and Tenascin-
R
Did not affect myelination
• Versican function in cochlea has not
been determined
http://atlasgeneticsoncology.org/Genes/GC_VCAN.html
11. Hypothesis
Versican expression in the cochlea is required for
• maintaining the structural integrity of auditory nerve
• functional recovery from cochlear damage.
12. Using Transmission Electron Microscopy (TEM) to view
morphological differences between WT and KO mice
• Mice TEM samples were WT and KO before noise
exposure
21. Conclusions
• Our audiograms signify a lack of recovery in the auditory nerve for
Versican knockout mice.
• Our TEM samples show delamination, axonal changes and other
irregularity of neuron structure in the knockout mice that may
cause the variances in recovery between WT and KO mice.
• These differences in morphology and threshold shift between WT
and KO mice suggest that Versican is important in damage recovery
and structural regularity in the auditory nerve.
22. Further Analysis of our Data
• How can better show that the
Versican KO mice are detecting less
sound after damage?
– Versican KO and WT mice have similar
thresholds
– Comparing amplitude of the first waveform
between KO and WT mice that can be
obtained from ABR results
• Investigate regression of recovery
for Versican KO mice
– Run statistical analysis for each mouse
23. Acknowledgements
o Dr. Hainan Lang
o Lab members
Yazhi Xing, LaShardai Conaway, Clarisse
Panganiban, Xin Liu, Andy Sheng, Kenyaria
Noble, Juhong Shu
o Nancy Smythe - TEM
o Dr. Mjaatvet Corey – VCAN mice
o Department of Pathology and Laboratory
Medicine
o The Medical University of South Carolina
o Randy LaCross and Christina Belis (SPRI)
o Dr. Jennifer Taylor