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AssigneeNone recorded
InventorsMichael V. Wiles, Christopher J. Kirk
Estimating the term…
The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a Glycerol Kinase gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.
A transgenic mouse comprising a disruption in a Glycerol Kinase gene.
A transgenic mouse comprising a disruption in a Glycerol Kinase gene, wherein there is no native expression of endogenous Glycerol Kinase gene.
A method of producing a transgenic mouse comprising a disruption in a Glycerol Kinase gene, the method comprising:
A targeting construct comprising:
A cell comprising a disruption in a Glycerol Kinase gene.
A method of identifying an agent that modulates a phenotype selected from the group consisting of neurological abnormality, an integumentary abnormality and a morphological abnormality, the method comprising:
A method of identifying an agent that modulates a phenotype selected from the group consisting of neurological abnormality, an integumentary abnormality and a morphological abnormality, the method comprising:
A method of identifying a potential therapeutic agent for the treatment of alopecia, the method comprising:
A method of identifying a potential therapeutic agent for the treatment of alopecia, the method comprising:
A method of evaluating a potential therapeutic agent capable of affecting a condition associated with a mutation in a Glycerol Kinase gene, the method comprising:
A method of evaluating a potential therapeutic agent capable of affecting a condition associated with a mutation in a Glycerol Kinase gene, the method comprising:
A therapeutic agent for treating alopecia, wherein the agent modulates Glycerol Kinase gene product.
A therapeutic agent for treating alopecia, wherein the agent is an agonist of Glycerol Kinase gene product.
A pharmaceutical composition comprising a Glycerol Kinase gene or Glycerol Kinase gene product.
A method of preparing a pharmaceutical composition for a condition associated with a function of Glycerol Kinase gene product, the method comprising:
Phenotypic data associated with a transgenic mouse comprising a disruption in a Glycerol Kinase gene, wherein the phenotypic data is in an electronic database.
Dependencies are inferred from the claim text.
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Genetically modified vertebrates, e.g. transgenic: knock-out vertebrates
Transferring phosphorus containing groups, e.g. kinases: phosphotransferases with an alcohol group as acceptor , e.g. protein kinases
For animal cells: for producing genetically modified animals, e.g. transgenic
Animals genetically altered by homologous recombination: maintaining or altering function, i.e. knock in
Term end not estimated
The present invention relates to transgenic animals, compositions and methods relating to the characterization of gene function.
Various conditions are associated with a glycerol kinase deficiency. A sequence was isolated showing similarity to glycerol kinase (GeneBank Accession No.: AW01236; GI: 5860914). As such gene may be important in biological and disease processes, a clear need exists for further in vivo characterization, which may aid in the identification and discovery of therapeutics and treatments useful in preventing, ameliorating or correcting dysfunctions or diseases.
Given the importance of kinases such as Glycerol Kinase (GenBank Accession No.: AW01236; GI: 5860914), a clear need exists for the elucidation of their functions, which information can be used in preventing, ameliorating or correcting dysfunctions or diseases associated therewith.
FIG. 1 shows the polynucleotide sequence for a murine Glycerol Kinase gene (SEQ ID NO:1).
FIG. 2 shows design of the gene trapping construct (DeltaGT) used to disrupt Glycerol Kinase genes. FIG. 2 also shows the genomic DNA sequence adjacent to the integration site of DeltaGT in mice Glycerol Kinase disruptions as determined by 5′RACE (SEQ ID NO:2).
FIG. 3 shows a graph relating to an average amount of force applied by a filament to a hindpaw in which a response, such as, for example, movement of the hindpaw, was recorded for historical wild-type mice and homozygous mutant mice during a mechanical sensitivity test.
The invention is based, in part, on the evaluation of the expression and role of genes and gene expression products, primarily those associated with a Glycerol Kinase gene. Among other uses or applications, the invention permits the definition of disease pathways and the identification of diagnostically and therapeutically useful targets. For example, genes that are mutated or down-regulated under disease conditions may be involved in causing or exacerbating the disease condition. Treatments directed at up-regulating the activity of such genes or treatments that involve alternate pathways, may ameliorate the disease condition.
Generation of Targeting Construct
The targeting construct of the present invention may be produced using standard methods known in the art. (see, e.g., Sambrook, et al., 1989, Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; E. N. Glover (eds.), 1985, DNA Cloning: A Practical Approach, Volumes I and II; M. J. Gait (ed.), 1984, Oligonucleotide Synthesis; B. D. Hames & S. J. Higgins (eds.), 1985, Nucleic Acid Hybridization; B. D. Hames & S. J. Higgins (eds.), 1984, Transcription and Translation; R. I. Freshney (ed.), 1986, Animal Cell Culture; Immobilized Cells and Enzymes, IRL Press, 1986; B. Perbal, 1984, A Practical Guide To Molecular Cloning; F. M. Ausubel et al., 1994, Current Protocols in Molecular Biology, John Wiley & Sons, Inc.). For example, the targeting construct may be prepared in accordance with conventional ways, where sequences may be synthesized, isolated from natural sources, manipulated, cloned, ligated, subjected to in vitro mutagenesis, primer repair, or the like. At various stages, the joined sequences may be cloned, and analyzed by restriction analysis, sequencing, or the like.