Method of screening for agents inhibiting chloride...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S023100, C435S069100, C435S070100, C530S350000

Reexamination Certificate

active

07125976

ABSTRACT:
The present invention isolates and characterizes the exc-4 gene ofC. elegans, and identifies exc-4 as an orthologue of the human CLIC family of chloride intracellular channels. Accordingly, a nucleic acid having the sequence of SEQ ID NO.: 1 is disclosed, as well as recombinant vectors and host cells comprising the nucleic acid sequence of SEQ ID NO.: 1. Further, a number of screening methods are disclosed to identify putative agents that inhibit vertebrate, and preferably human, CLICs usingC. elegansand exc-4 inhibition as a loss-of-function model for CLIC activity. Also disclosed is a method of determining whether a specific member of the CLIC gene family is involved in tubulogenesis, where the rescue of aC. elegansexc-4 excretory cell phenotype via expression of a transgenic CLIC gene of interest indicates that the CLIC gene of interest is involved in tubulogenesis. Finally, a method is disclosed of identifying putative vertebrate, and preferably human, CLIC inhibitors using transgenicC. elegansexc-4 mutant embryos, where expression of the transgene yields a CLIC product that rescues the exc-4 mutant phenotype. Agents of interest resulting in a reversionary exc-4 mutant phenotype are putative agents that inhibit CLIC expression or function.

REFERENCES:
patent: 6465715 (2002-10-01), Zwaal et al.
patent: WO 02/24872 (2002-03-01), None
Sulston, Accession No. AL 132876.4, Nov. 15, 1999.
Hogan, P. et al., “Organogenesis: Molecular Mechanisms of Tubulogenesis.” Nat. Rev. Genet. 3(7):513-23, 2000.
Lubarksky, M. et al., “Tube Morphogenesis: Making and Shaping Biological Tubules.” Cell 112(1):19-28, 2003.
J. Folkman and C. Haudenschild, “Angiogenesis in Vitro.” Nature 288(5791):5551-6, 1980.
G.E. Davis and C.W. Camarillo, An Alpha 2 Beta 1 Integrin-Dependent Pinocytic Mechanism Involving Intracellular Vacuole Formation and Coalescence Regulates Capillary Lumen and Tube Formation in Three-Dimentional Collagen Matrix. Exp. Cell Res. 224(1):39-51, 1996.
G.J. Beitel and M.A. Krasnow, “Genetic Control of Epithelial Tube Size in the Drosophila Tracheal System.” Development 127(15):3271-82, 2000.
R.J. Metzger and M.A. Krasnow, “Genetic Control of Branching Morphogenesis.” Science 284(5420):1635-9, 1999.
G. Manning and M.A. Krasnow, in the Development of Drosophila Melanogaster M. Bate and A. Martinez Arias, Eds., Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY, vol. 1:609-685, 1993 (N/A).
F.K. Nelson, et al., “Fine Structure of theCaenorhabditis elegansSecretory-Excretory System.” J. Ultrastruct. Res. 82(2):156-71, 1983.
F.K. Nelson and D.L. Riddle, “Functional Study of theCaenorhabditis elegansSecretory-Excretory System Using Lazer Microsurgery.” J. Exp. Zool. 231(1):45-56, 1984.
M. Buechner, “Tubes and the SingleC. elegansExcretory Cell.” Trends Cell. Biol. 12(10):479-84, 2002.
J.R. Wolff and T. Bar, “Seamless Endothelia in Brain Capillaries During Development of the Rat's Cerebral Cortex.” Brain Res. 41(1):17-24, 1972.
Hogan and Kolodziej, “Organogenesis: Molecular Mechanisms of Tubulogenesis.” Nat. Rev. Genet. 3(7):513-23, 2002 (N/A).
M. Buechner, et al., “Cystic Canal Mutants inCaenorhabditis elegansare Defective in the Apical Membrane Domain of the Renal (Excretory).” Cell. Dev. Biol. 214:227-241, 1999.
Harrop, et al., “Crystal Structure of a Soluble Form of the Intracellular Chloride Ion Channel CLIC (NCC27) at 1,4-A Resolution.” (N/A).
Ashley, et al., “Challenging Accepted Ion Channel Biology: p64 and the CLIC Family of Putative Intracellular Anion Channel Proteins.” Mol. Membr. Biol. 20:1-11, 2003.
Landry, et al., “Purification and Reconstitution of Chloride Channels from Kidney and Trachea.” Science 244:1469-72, 1989.
Li and Weinman, “Chloride Channels and Hepatocellular Function: Prospects for Molecular Identification.” Annu. Rev. Physiol. 64:609-633, 2002.
Jentsch, et al., “Molecular Structure and Physiological Function of Chloride Channels.” Physiol. Rev. 82(2):503-568, 2002.
Ronnov-Jessen, “Differential Expression of a Chloride Intracellular Channel Gene, CLIC4, in Transforming Growth Factor-Beta1-Mediated Conversion of Fibroblasts to Myofibroblasts.” Am. J. Pathol. 161:471-480, 2002.
Tamir, et al., “Secretogogue-induced Gating of Chloride Channels in the Secretory Vesicles of Parafollicular Cells.” Endocrinology 135(5):2045-2057, 1994.
Schlesinger, et al., “Characterization of the Osteoclast Ruffled Border Chloride Channel and its Role in Bone Resorption.” J. Biol. Chem. 272(30):18636-18643, 1997.
Valenzuela, et al., “The Nuclear Chloride Ion Channel NCC27 is Involved in Regulation of the Cell Cycle.” J. Physiol. 529(3):541-552, 2000.
Fernandez-Salas, et al., “p53 and Tumor Necrosis Factor Alpha Regulate the Expression of a Mitochondrial Chloride Channel Protein.” J. Biol. Chem. 274:36488-36497, 1999.
Fernandez-Salas, et al., “mtCLIC/CLIC4, an Organellular Chloride Channel Protein is Increased by DNA Damage and Participates in the Apoptotic Response to p53.” Mol. Cell Biol. 22:3610-3620, 2002.
Matthew Buechner, David Hall and Edward Hedgecock, “Exc Mutations Affect Apical Cytoskeleton.” (Early 1995 Intenational Worm Meeting, Abstract 320, 1995.) (N/A).
Suzuki, et al., “A Putative GDP-GTP Exchange Factor is Required for Development of the Excretory Cell inCaenorhabditis elegans.” EMBO Rep. 2:530-535, 2001.

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