# US 12,004,493 B2 · Late-onset Alzheimer's disease animal model and uses thereof

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- Number: US 12,004,493 B2
- Document ID: US12004493B2
- Status: Granted
- Kind: B2
- Application number: 16/429,978
- Filed: 2019-06-03
- Published: 2019-12-26
- Granted: 2024-06-11
- Earliest claimed: 2018-06-04
- Assignees: The Board of Regents of the University of Oklahoma
- Applicants: The Board of Regents of the University of Oklahoma
- Inventors: Hiroshi Yamada; Chinthalapally Rao
- Web page: https://patentgrep.com/patent/US12004493B2

## CPC

- A01K 67/0276: Knock-out vertebrates
- G01N 33/5058: {Neurological cells}
- G01N 33/5088: {of vertebrates}
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2217/20: Animal model comprising regulated expression system
- A01K 2217/206: Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
- A01K 2227/105: Murine
- A01K 2267/0312: Animal model for Alzheimer's disease
- G01N 2800/2821: Alzheimer
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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

An animal model (e.g., mouse) and method of use, and cell culture assay method, for characterizing or screening a test compound for its effect on late onset Alzheimer's disease (LOAD). The test compound may be used as a therapeutic agent for treatment of Alzheimer's disease (AD). The AD animal model may be haploinsufficient for Shugoshin 1 (Sgo1) gene, or may comprise a genetic modification enabling modulation of Sgo1 expression in the brain of the animal when exposed to an Sgo1 expression-modulating compound, such as tamoxifen. After the test compound is administered to the animal model, the presence or amount of an AD biomarker is assessed or measured.

## Claims

### Claim 1

An in vitro method for screening a test compound for its effect on amyloid β expression comprising the steps of:
(a) providing a cell culture of primary brain cells cultured from a mouse whose expression of Shugoshin 1 (Sgo1) gene has been genetically modified to enable modulation of Sgo1 expression in the brain of the mouse when exposed to an Sgo1 expression-modulating compound, wherein the mouse is a Sgo1-CRISPR-cre-lox mutant mouse and the Sgo1 expression-modulating compound is tamoxifen, wherein the cells of the cell culture are induced to accumulate amyloid-β due to inhibition or reduction of Sgo1 expression when the Sgo1 expression-modulating compound is added to the cell culture;
(b) contacting the culture of (a) with a test compound and tamoxifen,
(c) assaying the culture of (b) for the presence or amount amyloid β and comparing the culture of (b) with a control culture contacted with tamoxifen but not contacted with the test compound, wherein a reduction of amyloid β expression as compared to the control culture indicates that the test compound is effective in reducing amyloid β expression.