Gridlock nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods

Abstract

The invention provides a novel gene, gridlock, and its encoded protein. gridlock plays a role in vascular development and modeling, and a mutation in gridlock has been associated with an aortic arch disease, coarctation. Thus, gridlock nucleic acid molecules and polypeptides can be used in methods of diagnosing, treating, and preventing gridlock-related diseases and conditions, such as aortic arch diseases.

Description

PRIORITY INFORMATION [0001] This application is a divisional of, and claims priority from, U.S. Ser. No. 10 / 364,012, filed Feb. 10, 2003 (pending), which is a divisional of, and claims priority from, U.S. Ser. No. 09 / 705,534, filed Nov. 3, 2000 (U.S. Pat. No. 6,558,932), which claims priority from U.S. Ser. No. 60 / 163,903, filed Nov. 5, 1999 (now abandoned).STATEMENT AS TO FEDERALLY SPONSORED RESEARCH [0002] This research has been sponsored, in part, by grant numbers HL07208, RO1-RR0888, RO1-DK55383, and RO-HL49579 from the National Institutes of Health. The government may have certain rights in the invention.FIELD OF THE INVENTION [0003] This invention relates to cardiovascular diseases. BACKGROUND OF THE INVENTION [0004] The vascular system contains vessels that are morphologically and functionally distinct. For example, arteries carry oxygenated blood at high pressure from the heart, while veins serve as capacitance vessels for blood return. While some of the differences within t...

AI Technical Summary

Benefits of technology

[0022] In another aspect, the invention provides a method for preventing or ameliorating the effect of a gridlock deficiency by administering to a subject having a gridlock deficiency an expression vector including a nucleic acid molecule encoding a functional gridlock polypeptide. The nucleic acid molecule is operably linked to a promoter and the gridlock polypeptide is sufficient to prevent or ameliorate the effect of the gridlock deficiency.

[0023] In a related aspect, the invention provides a method for preventing or ameliorating the effect of a gridlock deficiency by administering a functional gridlock polypeptide to a subject having a gridlock deficiency. The gridlock polypeptide is sufficient to prevent or ameliorate the effect of the gridlock deficiency.

[0024] In a further aspect, the invention provides a method for preventing or ameliorating the effect of a gridlock excess by administering an antisense gridlock molecule to a subject having a gridlock excess. The antisense gridlock molecule is sufficient to prevent or ameliorate the effect of the gridlock excess.

[0025] In a related aspect, the invention provides a method for preventing or ameliorating the effect of a gridlock excess by administering a gridlock antibody to a subject having a gridlock excess. The gridlock antibody is sufficient to prevent or ameliorate the effect of the gridlock excess.

[0045] By an “antisense molecule,” as used herein in reference to nucleic acid molecules, is meant a nucleic acid molecule having a sequence that is complementary to at least 75 nucleotides, and preferably at least 100, 150, or 200 nucleotides, of the coding strand of a gene, such as a gridlock gene. An antisense nucleic acid molecule can be, for example, capable of preferentially lowering the production of a mutant gridlock polypeptide encoded by a mutant gridlock gene.

Problems solved by technology

The aorta, the main trunk of the systemic arterial network, is subject to several congenital and acquired disorders, that may lead to severe complications in infancy and adulthood.

Its effects often become more physiologically severe at birth, when closure of the ductus can exacerbate the restriction to aortic blood flow.

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