The overall objective of the proposed studies is to obtain information regarding the role of TULP1 in the retina. The applicant recently obtained evidence pointing to the TULP1 gene as a cause for autosomal recessive retinitis pigmentosa (ARRP). The protein product of this gene is specifically expressed in the retina, but little additional information regarding the function of this protein exists. RP is a hereditary blinding disorder afflicting thousands of people. The genetic etiology of RP is known for only about 20 percent of the cases and the biochemical pathways involved in causing the disease even less. The first specific aim of this application focuses on localizing TULP1 in the retina. Determining the cell type(s) expressing TULP1 will begin to give clues as to the function of the protein. Experiments designed to achieve aim one will be conducted using molecular techniques including in situ hybridization and immunohistochemistry.
The second aim i nvolves analyzing a transgenic mouse strain lacking a functional TULP1 gene. It will be important to evaluate the retina of these mice for possible pathologic changes that might correlate with those found in humans with TULP1 mutations. The last specific aim involves proving that identified defects in the TULP1 gene cause retinal degeneration. This will be done by attempting to rescue the TULP1 knock-out mice (assuming the mice degenerate) by re-introducing the wild-type gene and by generating transgenic mice expressing constructs containing known TULP1 mutations on the null background. Methods to evaluate all mice include funduscopy, light and electron microscopy, and electroretinography. Discovering information regarding the function of TULP1 will hopefully provide knowledge about pathways involved in retinal degeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32EY006915-02
Application #
6125059
Study Section
Special Emphasis Panel (ZRG1-VISA (03))
Project Start
1999-12-01
Project End
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
2
Fiscal Year
2000
Total Cost
$32,416
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Mandal, Amritlal; Shahidullah, Mohammad; Delamere, Nicholas A (2018) TRPV1-dependent ERK1/2 activation in porcine lens epithelium. Exp Eye Res 172:128-136
Shahidullah, Mohammad; Mandal, Amritlal; Delamere, Nicholas A (2017) A Role for Calcium-Activated Adenylate Cyclase and Protein Kinase A in the Lens Src Family Kinase and Na,K-ATPase Response to Hyposmotic Stress. Invest Ophthalmol Vis Sci 58:4447-4456
Delamere, Nicholas A; Mandal, Amritlal; Shahidullah, Mohammad (2016) The Significance of TRPV4 Channels and Hemichannels in the Lens and Ciliary Epithelium. J Ocul Pharmacol Ther 32:504-508
Shahidullah, Mohammad; Mandal, Amritlal; Wei, Guojun et al. (2014) Nitric oxide regulation of Na, K-ATPase activity in ocular ciliary epithelium involves Src family kinase. J Cell Physiol 229:343-52
Shahidullah, Mohammad; Mandal, Amritlal; Wei, Guojun et al. (2014) Nonpigmented ciliary epithelial cells respond to acetazolamide by a soluble adenylyl cyclase mechanism. Invest Ophthalmol Vis Sci 55:187-97
Shahidullah, Mohammad; Delamere, Nicholas A (2014) Connexins form functional hemichannels in porcine ciliary epithelium. Exp Eye Res 118:20-9
Shahidullah, Mohammad; Mandal, Amritlal; Delamere, Nicholas A (2009) Responses of sodium-hydrogen exchange to nitric oxide in porcine cultured nonpigmented ciliary epithelium. Invest Ophthalmol Vis Sci 50:5851-8
Shahidullah, Mohammad; To, Chi-Ho; Pelis, Ryan M et al. (2009) Studies on bicarbonate transporters and carbonic anhydrase in porcine nonpigmented ciliary epithelium. Invest Ophthalmol Vis Sci 50:1791-800
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