Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-08-06
2001-10-16
Eyler, Yvonne (Department: 1646)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S069100, C435S235100, C435S320100, C435S325000, C435S348000
Reexamination Certificate
active
06303768
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production and isolation of such polynucleotides and polypeptides. More particularly, the polynucleotides and polypeptides of the present invention have been identified as a G-protein-coupled receptors having stress associated and life span associated activities.
BACKGROUND OF THE INVENTION
Studies on the genetics of aging in a number of organisms including the yeast
Saccharomyces cerevisiae,
the roundworm
Caenorhabditis elegans,
and the fruit fly
Drosophila melanogaster
have revealed the role of metabolic capacity and resistance to stress in determining life span. One mode of modulation of longevity has been suggested to be signal transduction. Signal transduction has emerged as an important molecular mechanism underlying longevity. The results obtained from the study of these organisms are applicable to the dietary restriction paradigm in mammals. It is thought that many of the molecular characteristics identified from these studies will be of interest in determining the effect of diet and signal transduction in the life span of mammals. However, the identification and role of the genes and gene products responsible for modulating the life-span of organism are not yet fully understood. Accordingly, there is a desire to obtain and characterize life-span modulating genes in order to more fully understand the role of stress and life-span.
The effect of genes on life span in Drosophila has been established by selective breeding (Rose et al. Genetics, 97, 173-186 (1981)). However, that methodology involves the participation of multiple genes with additive and quantitative effects that can be difficult to unravel. A more incisive approach is to use single gene mutations. A search for life-extension mutants can lead to the identification of individual genes that regulate biological aging.
SUMMARY OF THE INVENTION
In a first embodiment, the present invention provides a substantially purified Methuselah (MTH) polypeptide having an amino acid sequence as set forth in SEQ ID NO:2.
In another embodiment, the present invention provides an isolated polynucleotide encoding an amino acid sequence as set forth in SEQ ID NO:2. The isolated polynucleotide is selected from the group consisting of SEQ ID NO:1; SEQ ID NO:1, wherein T can also be U; a nucleic acid sequence complementary to SEQ ID NO:1; and fragments of a), b), or c) that are at least 15 bases in length and that hybridize under stringent conditions to DNA which encodes the polypeptide of SEQ ID NO:2.
In another embodiment, the present invention provides an expression vector containing an mth polynucleotide. The vector can be for example, a plasmid or a viral vector.
In yet another embodiment, the present invention provides a host cell transformed with an expression vector containing an mth polynucleotide.
In yet a further embodiment, the present invention provides a method of producing an MTH polypeptide by transforming a host cell with an mth polynucleotide; expressing the polynucleotide in the host; and recovering the MTH polypeptide.
In another embodiment, an antibody that binds to the polypeptide of SEQ ID NO:2 is provided. The antibody can be polyclonal or monoclonal.
The present invention also provides a method for identifying a compound which modulates mth expression or activity comprising: incubating components comprising the compound and an MTH polypeptide, or a recombinant cell expressing an MTH polypeptide under conditions sufficient to allow the components to interact; and determining the effect of the compound on the expression or activity of the gene or polypeptide, respectively.
In yet another embodiment, the present invention provides a method of detecting an mth-specific cell component in a sample comprising: contacting a sample suspected of containing mth with a reagent that binds to the mth-specific component; and detecting binding of the reagent to the component.
In yet a further embodiment, the present invention provides a method of promoting insect cell survival in vitro comprising contacting the cell with a survival promoting amount of a compound containing an MTH polypeptide or a agent capable of modulating MTH activity or expression.
In yet another embodiment, the present invention provides a method of producing a non-human organism having an increased life span comprising: introducing a transgene disrupting or interfering with expression of Methuselah (mth) into germ cells of a pronuclear embryo of the organism; implanting the embryo into the oviduct of a pseudopregnant female thereby allowing the embryo to mature to full term progeny; testing the progeny for presence of the transgene to identify transgene-positive progeny; and cross-breeding transgene-positive progeny to obtain further transgene-positive progeny.
In yet another embodiment, the present invention provides a transgenic organims having a phenotype characterized by an increase in mass or an increase in life span or an increase in resistance to a biologic stress. The organism may be any non-human organsims, including, for example, bovine, porcine and invetebrates, such as Drosophila.
In another embodiment, the present invention provides a method of increasing the life span of a subject, comprising: administering to the subject, a reagent which affects mth activity or expression.
In yet a further embodiment, the present invention provides a kit useful for the detection of an MTH polypeptide, the kit comprising a carrier containing one or more containers comprising a further container containing a mth binding reagent.
These and other aspects of the present invention will be apparent to those of skill in the art from the teachings herein.
REFERENCES:
Image consortium, Accession number AA250332, Mar. 12, 1997.*
Lin et al., Extended Life-Span and Stress Resistance in the Drosophila Mutant methuselah. Science 1998, vol. 282, pp. 943-946.*
Arking et al., Elevated Paraquat Resistance Can Be Used as a Bioassay for Longevity in a Genetically Based Long-Lived Strain of Drosophila. Dev. Genet. 1991, vol. 12, pp. 362-370.
Benzer Seymour
Lin Yi-Jyun
Andres Janet L.
California Institute of Technology
Eyler Yvonne
Fish & Richardson P.C.
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