# Core B: Mouse models Core

> **NIH NIH P01** · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · 2021 · $461,737

## Abstract

ABSTRACT
The use of transgenic and gene knock-out genetically engineered animals is a powerful and informative
approach that has been successfully undertaken by Core B in previous cycles to study neurodegenerative
diseases. Core B provides Projects 1-4 with appropriately genotyped and aged mouse models of risk-factors
for endosomal-lysosomal and autophagic abnormalities observed in Alzheimer's disease (AD) and Down
syndrome (DS). A particular focus is the breeding of mouse models that reproduce a broad range of
pathobiological phenotypes relevant to late-onset AD, especially related to the lysosomal network. Core B also
serves to acquire novel animal models with these pathologies, and to generate novel crosses between these
models and transgenic, knockin, or knockout models that carry or lack genes expected to affect AD-related
pathologies. The models either express or are deficient of factors that are mechanistically linked to endosomal-
lysosomal and autophagy pathology in all forms of AD, including the accumulation of the β-site cleaved
carboxyl-terminal fragment of the amyloid β precursor protein (βCTF), such as in a mouse model of DS; the
apolipoprotein E (ApoE) ε4 allele, the strongest genetic risk factor for late-onset AD; hyperactivation of rab5,
the key mediator of endosome dysfunction in AD; and altered cholesterol levels, studied by high fat and
cholesterol diet. Models of lysosomal abnormalities in AD will include loss-of-function of the presenilin 1 or 2
(PS1 and PS2) gene as well as high cholesterol diet. This Program Project focuses on the sources and
mechanisms that lead to endosomal pathology (Project 1 and 4), lysosome and autophagy dysfunction
(Projects 2 and 4), and exocytosis (Project 3), using multiple mouse models, many of which are shared by
more than one project. The Core Leader has extensive experience managing a large mouse colony with
complex breeding schemes, and will be able to coordinate animal breeding, genotyping, and delivery to
Projects 1-4.

## Key facts

- **NIH application ID:** 10126774
- **Project number:** 5P01AG017617-20
- **Recipient organization:** NATHAN S. KLINE INSTITUTE FOR PSYCH RES
- **Principal Investigator:** EFRAT LEVY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $461,737
- **Award type:** 5
- **Project period:** 2000-02-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126774

## Citation

> US National Institutes of Health, RePORTER application 10126774, Core B: Mouse models Core (5P01AG017617-20). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10126774. Licensed CC0.

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