Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal
Reexamination Certificate
1994-02-23
2001-04-17
Crouch, Deborah (Department: 1632)
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
Transgenic nonhuman animal
C800S015000, C800S017000, C800S018000
Reexamination Certificate
active
06218596
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates the c-ski gene. In particular, the present invention relates to DNA segments encoding chicken c-ski protein, to DNA constructs comprising the DNA segments and to cells transformed therewith. The present invention further relates to animals having increased muscle size and/or reduced amounts of fat.
2. Background Information
Viruses that contain the v-ski oncogene are not only capable of causing morphological transformation in vitro, but also can induce myogenic differentiation (Stavnezer et al., 1981, J. Virol. 39, 920-934; Li et al., 1986, J. Virol. 57, 1065-1072; Stavnezer et al., 1986, J. Virol. 57, 1073-1083; Colmenares and Stavnezer, 1989, Cell 59, 293-303). Viruses that carry and express c-ski cDNAs also induce foci and myogenic differentiation (Sutrave et al., 1990, Mol. Cell. Biol. 10, 3137-3144). This suggests the possibility that the ski oncogene is bifunctional since the two known functions of ski, transformation and differentiation, would appear to be contradictory properties. Using a v-ski probe, genomic clones for c-ski have been isolated and partially sequenced (Stavnezer et al., 1989, Mol. Cell. Biol. 9, 4038-4045). Comparisons of the properties of two forms of c-ski that are related by alternative splicing, and of several v-ski and c-ski deletion mutants have shown that the portions of ski required for transformation and differentiation are quite similar. These results suggest that the ability of c-ski and v-ski to cause transformation and induce differentiation may be related aspects of a single property of ski rather than two separate functions.
Relatively little is known about the biochemical functions of the ski proteins. All of the biologically active forms of c-ski and v-ski that have been studied are localized primarily in the nucleus (Barkas et al., 1986, Virology 151, 131-138; Sutrave et al., 1990, Mol. Cell. Biol. 10, 3137-3144). When the c-ski proteins are overexpressed in chicken cells, different forms of c-ski differ in their subnuclear localization; however, the significance of these differences, if any, is as yet unclear. when chromatin condenses for cell division, the over-expressed c-ski proteins are associated with the condensed chromatin (Sutrave et al., 1990, Mol. Cell. Biol. 10, 3137-3144). Biochemical studies have also shown that at least one form of c-ski can bind to DNA in the presence of other proteins (Nagase et al., 1990, Nucl. Acids Res. 18, 337-343).
None of the available data make it possible to infer the normal function of c-ski either in terms of its role in growth and development (if any) or to have any direct insight into its mode of action.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an isolated and characterized c-ski cDNA.
It is another object of the present invention to provide a gene that increases the muscle size in animals.
It is another object of the present invention to provide domestic livestock with increased muscle size and decreased fat tissue.
It is a further object of the present invention to provide a treatment for patients suffering from serious muscle injury or muscle degenerative diseases.
It is a further object of the present invention to provide a treatment for patients suffering from obesity.
Various other objects and advantages of the present invention will be apparent from the drawings and the following description of the invention.
In one embodiment, the present invention relates to a DNA segment encoding a chicken c-ski protein or a DNA fragment complementary to said segment.
In another embodiment, the present invention relates to a DNA construct comprising a DNA segment encoding a chicken c-ski protein and a vector. In a further embodiment, the present invention relates to a DNA construct comprising a DNA segment encoding a truncated chicken c-ski protein having the function of c-ski and a vector. The present invention also relates to host cells stably transformed with either one of the two DNA constructs described above, in a manner allowing expression of the protein encoded in the construct.
In yet another embodiment, the present invention relates to a animal having increased muscle size, all of whose cells contain a DNA construct comprising a DNA segment encoding a ski protein and a vector, introduced into the animal, or an ancestor of the animal. The DNA segment may encode the entire protein or a truncated version thereof.
In further embodiment, the present invention relates to an animal having increased muscle size and/or reduced fat, all of whose cells contain a DNA construct comprising a DNA segment encoding a truncated ski protein having the function of ski and a vector, introduced into the animal, or an ancestor of the animal.
In another embodiment, the present invention relates to a method of stimulating muscle growth or preventing muscle degeneration comprising delivering a DNA construct of the present invention to the muscle under conditions such that the protein of the construct is expressed and muscle growth induced.
In a further embodiment, the present invention relates to a method of treating a muscle degenerative disease comprising delivering a DNA construct of the present invention to the effected muscle under conditions such that the protein of the construct is expressed and treatment effected.
REFERENCES:
patent: 4736866 (1988-04-01), Leder et al.
Palmiter et al., Proc. Natl. Acad. Sci. 88:478-482 (1991).*
Kappel et al., Curr. Opin. Biotech. 3:548-553 (1992).*
Pursel et al., J. Reprod. Fert. Suppl. 40:235-245 (1990).*
Shamay et al., Transgenic Research 1:124-132 (1992).*
Li et al., J. Virology 57(3): 1065-1072 (1986).*
Wilmut et al., New Scientist, Jul. 7, 1988, pp. 56-59.*
Van Brunt, BioTechnology 6(10): 1149-1154 (1988).
Hughes Stephen H.
Pursel Vernon
Sutrave Pramod
Crouch Deborah
The United States of America as represented by the Department of
Townsend and Townsend / and Crew LLP
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