Growth arrest homebox gene

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

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435243, 4353201, 435325, 536 235, C12N 1512, C12N 1563, C12N 121, C12N 510

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058561218

ABSTRACT:
A novel growth arrest homeobox gene has been discovered and the nucleotide sequences have been determined in both the rat and the human. The expression of the novel homeobox gene inhibits vascular smooth muscle cell growth. The growth arrest homeobox gene hereinafter referred to as the "Gax gene" and its corresponding proteins are useful in the study of vascular smooth muscle cell proliferation and in the treatment of blood vessel diseases that result from excessive smooth muscle cell proliferation, particularly after balloon angioplasty.

REFERENCES:
patent: 5302706 (1994-04-01), Smith
Nabel et al Science 249:1285-1288 (1990).
Donald B. Smith, et al., Single-Step Purification of Polypeptides Expressed in Escherichia coli as Fusions with Gluthathione S-tranferase, Gene 67: 31-40 (1988).
Moshe Y. Flugelman, MD, et al., Low Level in Vivo Gene Transfer into the Arterial Wall Through a Perforated Balloon Catheter, Circulation 85: 1110-1287 (1992).
"The Growth Arrest-Specific Gene, gas1, is Involved in Growth Suppression," Del Sal et al., International Centre for Genetic Engineering and Biotechnology Aug. 21, 1992, pp. 595-607.
"Cloning of Senescent Cell-Derived Inhibitors of DNA Synthesis Using an Expression Screen", Noda et al. Experimental Cell Research, 211, 1994 pp. 90-98.
"CHOP" (GADD153) and its Oncogenic Variant, TLS-CHOP, Having Opposing Effects on the Induction of G.sub.1 /S Arrest, Barone et al. Genes & Development, 8, 1994, pp. 453-464.
"Mox-1 and Mox-2 Define a Novel Homebox Gene Subfamily and are Differentially Expressed during Early Mesodermal Patterning in Mouse Embryos", Candia et al., Development, 116, Aug. 28, 1992, pp. 1123-1136.
"Arterial Gene Transfer Using Pure DNA Applied Directly to a Hydrogel-Coated Angioplasty Balloon," Riessen et al., Human Gene Therapy, 4, 1993, pp. 749-758.
Antisense c-myb Oligonucleotides Inhibit Intimal Arterial Smooth Muscle Cell Accumulation in Vivo, Simons et al. Nature, vol. 359, Sep. 3, 1993, pp. 67-70.
"Site-Specific Gene Expression In Vivo by Direct Gene Transfer Into the Arterial Wall", Nabel et al. Reports, Apr. 11, 1990, pp. 1285-1288.
Exhibit A is the gene sequence for the rat Gax cDNA (2244 base pairs) submitted by Kenneth Walsh, released to the public Feb. 28, 1993.
Exhibit B.sub.1 is a gene sequence for Mox-1 (2182 base pairs) (mistakenly designated "Mox-2") submitted by A.F. Candia to New GenBank and created on Sep. 25, 1992.
Exhibit B.sub.2 is the same gene sequence as Exhibit B.sub.2 except the former designation "Mox-2" has been corrected to read Mox-1.
Exhibit C is the partial gene sequence for mouse Mox-2A submitted by Candia A by A.F. Candia to GenBank and created on Oct. 5, 1992.
Exhibit D is the revision of Exhibit C to show the 1440 base pair mouse Mox-2 sequence on Mar. 6, 1993.
Candia et al., Nucleic Acids Research (1993) 21(21):4982.
"Molecular Cloning of a Homeobox Transcription Factor From Adult Aortic Smooth Muscle", Patel et al., The Journal of Biological Chemistry, vol. 267, No. 36, Dec. 25, 1992, pp. 26085-26090.
"Molecular Cloning of a Diverged Homeobox Gene that is Rapidly Down-Regulated During the G.sub.0 /G.sub.1 Transition in Vascular Smooth Muscle Cells", Gorski et al., Molecular And Cellular Biology, vol. 13, No. 6, Jun. 1993, pp. 3722-3733.
"Homeobox Transcription Factor Regulation in the Cardiovascular System", Gorski et al., TCM, vol. 3, No. 5, 1993, pp. 184-190.
"Cloning and Sequence Analysis of Homeobox Transcription Factor CDNAs With an Inosine-Containing Probe", Gorski et al. Short Technical Reports, vol. 16, No. 5, 1994.

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