# US 2010/0169985 A1 · Transgenic Mouse Models for Diseases Caused by mtDNA Mutations and Related Methods > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0169985 A1 - Document ID: US20100169985A1 - Status: Published application - Kind: A1 - Application number: 12/205,588 - Filed: 2008-09-05 - Published: 2010-07-01 - Earliest claimed: 2007-09-05 - Assignees: The Regents of the University of California - Inventors: Douglas C. Wallace; Wei Wei Fan; Katrina G. Waymire - Web page: https://patentgrep.com/patent/US20100169985A1 ## CPC - A01K 67/0275: Genetically modified vertebrates, e.g. transgenic - A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure} - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 15/10: for impotence - A61P 17/14: for baldness or alopecia - C12N 15/8509: {for producing genetically modified animals, e.g. transgenic} - A01K 2217/052: inducing gain of function - A01K 2227/105: Murine - A01K 2267/03: Animal model, e.g. for test or diseases - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Animal models and methods wherein homoplasmic and heteroplasmic mtDNA mutation(s) are induced in an animal (e.g., a mouse) to cause or facilitate the development of a disorder (e.g., disease, malformation, defect, abnormality or other disorder). In at least some embodiments, the mtDNA mutation(s) will cause or facilitate the development of an age-related disorder, such as a cardiac disease, cardiomyopathy, muscle disease, cancer, abnormaly in tissues of high cellular turnover, heart dysfunction, graying of hair, alopecia, auditory function loss, cochlear degeneration, immune cell loss, anemia, male germ cell loss leading to lack of sperm and infertility, skeletal muscle mass loss (sarcopenia), neurodegeneration, increased presence of apoptotic markers, and loss of bone mass. ## Claims ### Claim 1 A transgenic mouse model for a disorder caused by a mitochondrial DNA point mutation, said mouse model comprising a mouse having a mtDNA missense mutation that causes or facilitates the development of the disorder. ### Claim 2 (depends on 1) A mouse model according to claim 1 wherein the mouse has a mtDNA ND6-COI double mutation. ### Claim 3 (depends on 1) A mouse model according to claim 1 comprising a mouse having a homoplasmic mtDNA missense mutation. ### Claim 4 (depends on 1) A mouse model according to claim 1 comprising a mouse having a heteroplasmic mtDNA missense mutation. ### Claim 5 (depends on 4) A mouse model according to claim 4 wherein the mouse has mtDNAs from NZB and 129 mouse strains mixed in the same cytoplasm. ### Claim 6 (depends on 1) A mouse model according to claim 1 wherein the disorder is an aging-related disorder. ### Claim 7 (depends on 1) A mouse model according to claim 1 wherein the disorder is selected from the group consisting of: cardiac disease, cardiomyopathy, muscle disease, cancer, abnormalities in tissues of high cellular turnover, heart dysfunction, graying hair, alopecia, auditory function loss, cochlear degeneration, immune cell loss, anemia, male germ cell loss leading to lack of sperm and infertility, skeletal muscle mass loss (sarcopenia), neurodegeneration, increased presence of apoptotic markers, and loss of bone mass. ### Claim 8 (depends on 1) A mouse model according to claim 1 wherein the disorder is hypertrophic cardiomyopathy and wherein the mouse is a homoplasmic COI T6589C missense mutant mouse. ### Claim 9 (depends on 8) A mouse model according to claim 8 wherein the mouse has mtDNA that is homoplasmic for a COI missense mutation (T6589C), 50-50 heteroplasmic for an ND6 C insertion frameshift mutation (13885insC) and has a T deletion reversion of that mutation (13885insCdelT). ### Claim 10 (depends on 8) A mouse model according to claim 8 wherein the mouse is a female mouse that has been backcrossed to C57BL/6J males. ### Claim 11 (depends on 1) A method for determining potential effectiveness of a test therapy in treating, delaying the onset of or lessening the severity of a disorder that is caused or facilitated by an mtDNA missense mutation, said method comprising the steps of: A) providing a mouse model according to claim 1; B) administering the test therapy to the mouse; and C) determining whether the test therapy was effective in treating, delaying the onset of or lessening the severity of the disorder, or of a symptom of the disorder, compared to an untreated mouse model. ### Claim 12 (depends on 11) A method according to claim 11 wherein the test therapy comprises a drug. ### Claim 13 (depends on 11) A method according to claim 11 wherein the test therapy comprises a chemical composition. ### Claim 14 (depends on 11) A method according to claim 11 wherein the test therapy comprises a biologic. ### Claim 15 (depends on 11) A method according to claim 11 wherein the test therapy comprises a vaccine. ### Claim 16 (depends on 11) A method according to claim 11 wherein the test therapy comprises a therapeutic device.