# US 9,040,771 B2 · Nonhuman mammal whose mtDNA is from a nonhuman mammal resistant to a selected disease or disorder and whose nDNA is from a nonhuman donor mammal more susceptible to the selected disease or disorder

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- Number: US 9,040,771 B2
- Document ID: US9040771B2
- Status: Granted
- Kind: B2
- Application number: 13/360,344
- Filed: 2012-01-27
- Published: 2014-09-04
- Granted: 2015-05-26
- Earliest claimed: 2008-06-27
- Assignees: The UAB Research Foundation
- Applicants: Scott Webster Ballinger; Danny R. Welch; Robert Allen Kesterson; Larry W. Johnson
- Inventors: Scott Webster Ballinger; Danny R. Welch; Robert Allen Kesterson; Larry W. Johnson
- Web page: https://patentgrep.com/patent/US9040771B2

## CPC

- 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}
- A01K 67/0271: Chimeric vertebrates, e.g. comprising exogenous cells
- A01K 67/0273: Cloned vertebrates
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A61D 19/04: for embryo transplantation
- G01N 33/5023: {on expression patterns}
- A01K 2217/00: Genetically modified animals
- A01K 2227/10: Mammal
- A01K 2227/105: Murine
- A01K 2267/0331: Animal model for proliferative diseases
- A01K 2267/0375: Animal model for cardiovascular diseases
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61D: VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided herein are mitochondrial-nuclear exchanged cells and animals comprising mitochondrial DNA (mtDNA) from one subject and nuclear DNA (nDNA) from a different subject. Methods for producing a mitochondrial-nuclear exchanged animal and animals made by the methods are provided. Also provided are methods of screening for agents useful for treating a disease or disorder using mitochondrial-nuclear exchanged animals or cells, tissues or organs thereof.

## Claims

### Claim 1

A nonhuman mammalian zygote or a nonhuman mammalian embryo whose cell or cells comprise mitochondrial DNA (mtDNA) from a first nonhuman donor mammal resistant to a selected disease or disorder and comprise nuclear DNA (nDNA) entirely from a second nonhuman donor mammal more susceptible to the selected disease or disorder compared to the first nonhuman mammal, wherein the donor resistant to the selected disease or disorder and the donor susceptible to the selected disease or disorder exhibit distinct mtDNA haplotypes.

### Claim 2 (depends on 1)

The nonhuman mammalian zygote or nonhuman mammalian embryo of claim 1, whose cell or cells comprise mtDNA entirely from a first nonhuman donor mammal resistant to the selected disease or disorder.

### Claim 3 (depends on 1)

The zygote or embryo of claim 1, wherein the disease or disorder is selected from the group consisting of cancer, cardiovascular disease, diabetes, neurological disorder, aging, metabolic disorder, immune disorder, obesity, and musculoskeletal disorder.

### Claim 4 (depends on 1)

The embryo of claim 1, wherein the embryo is a pro-nuclear embryo.

### Claim 5 (depends on 1)

A nonhuman mammal that develops from the embryo of claim 1, wherein the cells of the mammal comprise mtDNA from a first nonhuman donor mammal resistant to a selected disease or disorder and comprise nDNA entirely from a second nonhuman donor mammal more susceptible to the selected disease or disorder compared to the first nonhuman mammal, wherein the donor resistant to the selected disease or disorder and the donor susceptible to the selected disease or disorder exhibit distinct mtDNA haplotypes.

### Claim 6 (depends on 5)

The nonhuman mammal of claim 5, whose cells comprise mtDNA entirely from a first nonhuman donor mammal resistant to the selected disease or disorder.

### Claim 7 (depends on 5)

The nonhuman mammal of claim 5, wherein the mammal is a mouse comprising mtDNA from NZB/B1NJ mice.