# Novel immune deficient mouse models of Huntington's disease

> **NIH NIH R24** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $602,990

## Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease for which there is
currently no available cure. Before cell therapies can be introduced into the clinic, efficacy must first
be shown in animal models of the disease. Although excellent murine models of HD exist, efficacy
testing of human stem cell products in transgenic mouse models is challenged by a xenogeneic
immune response in the animal which causes rejection of the human cells. We have developed two
immune deficient and xeno-tolerant mouse models of Huntington's disease to allow efficacy testing of
human cell-based therapies Our hypothesis is that our novel YAC128/NSG and R6/NSG strains that
we are characterizing will provide xeno-tolerant Huntington's disease mouse models capable of
retaining human stem cell products while displaying phenotypic disease progression for efficacy
testing of proposed therapies. Huntington's disease transgenic mouse strains that lack an
immune system could provide a powerful model for proof of efficacy testing of candidate
human adult and pluripotent cell therapies for HD patients.
The mice have been generated and we are now poised for further testing and characterization, plus
expansion for distribution. Both strains of mice have the characteristic aggregates in their brain tissue.
The normally very short-lived R6 strain has a significantly prolonged lifespan, in the absence of an
immune system, further implicating the role of the immune system in disease progression.
In Aim 1 we will continue to expand and fully characterize the two new strains of mice. In Aim 2 we will
assess permissiveness for human stem/progenitor cell retention in the brain. In Aim 3 we will
determine whether the immune deficient HD mice have the presence of the well characterized HD
phenotypes observed in the parental strains, using behavioral and phenotypic assays established in
our laboratory. In Aim 4 we will humanize R6/2/NSG and YAC128/NSG pups at birth to create
relevant models to study the human immune system response to anti-Htt therapies in the pipeline to
treat HD and Juvenile HD. The humanization of these strains could provide valuable insight into
the role of the human immune system in HD progression, and will be useful models in which to
perform anti- htt drug, viral vector, gene editing, and antibody testing.

## Key facts

- **NIH application ID:** 9843748
- **Project number:** 5R24OD021606-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Joseph Anderson
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $602,990
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843748

## Citation

> US National Institutes of Health, RePORTER application 9843748, Novel immune deficient mouse models of Huntington's disease (5R24OD021606-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9843748. Licensed CC0.

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