# A TRANSOMIC MOUSE MODEL FOR ALZHEIMER'S DISEASE

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 1991 · $158,773

## Abstract

Alzheimer's disease (AD) is a common dementia with characteristic
neuropathology.  Although a number of animal models have been proposed
which exhibit some of the neurochemical and pathological abnormalities seen
in AD, there is no model which can be utilized to definitively study the
pathogenesis and treatment of this disease.  We propose to develop a
transgenic mouse model of AD in which selected chromosomal regions, thought
to contain the disease-causing gene(s), are dissected from patients with
familial Alzheimer's disease (FAD) and inserted into the germ line of
recipient mice ("transomic mice").  We have developed the methodology to
precisely microdissect chromosome bands and microinject the dissected
genomic DNA, in its natural context, into fertilized mouse ova.  The
regions to be microdissected from chromosomes from tissue culture cells are
21q11-q22 in patients with early onset FAD (with and without an amyloid
precursor protein (APP) 717 mutation) and 19q13 from patients with late
onset FAD.  Experiments will be performed in which dissected fragments from
chromosome 21 will contain both the putative FAD locus and the APP gene, as
well as experiments in which the FAD locus and APP gene are dissected
separately and microinjected into mouse embryos.  The identical regions
will be dissected from normal individuals as a control for gene dosage.
21q11-q22 will also be dissected from Dutch patients with hereditary
cerebral hemorrhage with amyloidosis (HCHA-D) to determine if different APP
mutations induce varying phenotypes in transgenic mice.  Live births from
infected embryos will be screened for human sequences using a PCR method to
detect human specific Alu sequences, and heterozygous and homozygous
transomic mouse strains developed by selective matings.  Brains of
transomic mice will be examined in detail for neuropathologic lesions,
particularly senile plaques and neurofibrillary tangles, and by
immunohistochemistry for astrocytosis and beta amyloid deposition.  DNA
from transomic mouse strains exhibiting neuropathology will be studied with
respect to the organization and expression of specific human sequences
(particularly the APP gene) using filter hybridization techniques as well
as determining the location of human sequences in the transomic mouse
genome using in situ hybridization.  In summary, this methodology has the
potential of establishing a legitimate mouse model for AD and to
unambiguously identify regions of the human chromosome map which cause
specific neuropathology in FAD.

## Key facts

- **NIH application ID:** 3122632
- **Project number:** 1R01AG010683-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **SAM.gov UEI:** M746VC6XMNH9
- **Principal Investigator:** MICHAEL V VIOLA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $158,773
- **Award type:** 1
- **Project period:** 1991-09-29 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122632

## Citation

> US National Institutes of Health, RePORTER application 3122632, A TRANSOMIC MOUSE MODEL FOR ALZHEIMER'S DISEASE (1R01AG010683-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122632. Licensed CC0.

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