DNA molecule encoding a mutant prepro-neuropeptide Y, a mutant s

Details DNA molecule encoding a mutant prepro-neuropeptide Y, a mutant s DNA molecule encoding a mutant prepro-neuropeptide Y, a mutant s

1997-12-19

2000-04-04

Campell, Bruce R.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

435 6, 4352523, 4353201, 435325, 435455, 536 231, C07H 2104, C12N 1500, C12N 1563, C12N 1585

Patent

active

060463171

ABSTRACT:
The invention relates to a DNA sequence comprising a nucleotide sequence encoding a prepro-neuropeptide Y (PreproNPY) where the leucine amino acid in position 7 of the signal peptide part of said preproNPY has been replaced by proline. The invention concerns further the mutant signal peptide as such or associated with any other cleavage product of preproNPY, methods for the determination, in a biological sample, of said DNA sequence or said peptide. Furthermore, this invention relates to a method for diagnosing a predisposition for increased serum cholesterol or LDL cholesterol level in a human subject, and to methods for treating a human subject diagnosed for predisposition for increased serum cholesterol or LDL cholesterol. Transgenic animals carrying either the mutant sequence or the normal sequence are also within the scope of this invention.

REFERENCES:
patent: 5455164 (1995-10-01), Turner
Minth et al. Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proc. Natl. Acad. Sci. USA 81:4577-4581, Jul. 1984.
Erickson et al. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274:1704-1707, Dec. 1996.
Jaenisch, R. Transgenic animals. Science 240: 1468-1474 Jun. 1988.
Larhammar et al. Structure and expression of the rat neuropeptide Y gene. Proc. Natl. Acad. Sci. USA 84: 2068-2072, Apr. 1987.
Uusitupa, M.I.J. et al. (1988). "Neuropeptide Y: a novel link between the neuroendocrine system and cholesterol metabolism." Ann. Med. 30:508-510.
Karvonen, M.K. et al. (1988). "Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with hihg serum cholesterol and LDL cholesterol levels." Nature Genetics 4:1434-1437.
Roche, C. et al. (1997). "Genetic studies of neuropeptide Y and neuropeptide Y receptors Y1 and Y5 regions in morbid obesity." Diabetologia 40:671-675.
Thorsell, A. et al. (1996). "Cationic lipid-mediated delivery and expression of prepro-neuropeptide Y cDNA after intraventricular administration in rat: feasibility and limitations." Regulatory Peptides 61:205-211.
Nystrom, F. et al. (1996). "A Population Study of Plasma Neuropeptide Y: Correlations with Components of the Metabolic Syndrome." Blood Pressure 5:349-353.

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