# Creation of a polygenic humanized mouse model for HIV-1

> **NIH NIH U42** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $480,835

## Abstract

PROJECT SUMMARY
This funding request is a one-year administrative supplement to NIH Grant U42 OD012210 for the UC Davis
Mutant Mouse Resource and Research Center (MMRRC). It will be used to create and validate a unique and
“highly” impactful polygenic humanized mouse model for human immunodeficiency virus type one (HIV-1)
therapeutics, prevention, and cure. Prior attempts to generate an HIV-1 mouse model by random transgenesis
have failed. What is now proposed through CRISPR/Cas9 will overcome past limitations. This strategy enables
genomic insertion of human coding sequence into orthologous mouse loci, rendering gene expression under
promoter and enhancer elements in a physiologically spatial and temporal manner. These modifications will, for
the first time, recapitulate what is required for human cell susceptibility to productive and restrictive HIV-1
infection. Such unimpeded viral growth in mouse cells will facilitate novel preventative, therapeutic and cure
strategies. To that end, we will generate knockins of human coding sequences for CD4 and CCR5 and an
aspartic acid to glycine (D106G) modification of C1qbp in the orthologous genomic mouse loci. These genetic
modifications will result in a humanized polygenic (hCD4/hCCR5/C1qbp[D106G]) expressing mouse with
deactivation of the corresponding mouse genes. This mouse will permit, for the first time, productive viral infection
in CD4+ T cell and monocyte-macrophages, immune suppression, end organ disease, and response(s) to
antiretroviral and immune-based preventative therapies as seen after human infection. Model creation and
deposition into the MMRRC (K Lloyd, UC Davis) and validation for therapeutics, prevention and cure (H
Gendelman, UNMC) will be completed by January 31, 2023. Both creation and validation of the new HIV-1
mouse models as proposed herein are within the scope of the parent award to the MMRRC when such models
are not available in public repositories, there is strong scientific justification, and research and validation
expertise is not broadly available. There are four unique aspects to this project: (1) Creation of a unique polygenic
humanized mouse model unavailable elsewhere in the world that express together all three proteins (CD4,
CCR5, and C1qbp[D106G]) necessary for HIV binding, entry, and activation in human cells; (2) Verification of
expression of human coding sequences into the orthologous mouse loci and the absence of expression of the
corresponding mouse genes following the highest quality control standards and principles of scientific rigor and
reproducibility; (3) Validation of the model by testing in studies of viral prevention, therapeutics and cure studies,
and (4) Sharing of this new and fully validated HIV mouse model, data, and testing platforms with the biomedical
research community without limitations or restrictions. The outcomes of this project…unique model, experimental
data, validation protocols and conditions will contribute significantly to our a...

## Key facts

- **NIH application ID:** 10581244
- **Project number:** 3U42OD012210-23S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** KC KENT LLOYD
- **Activity code:** U42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $480,835
- **Award type:** 3
- **Project period:** 1999-09-30 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10581244

## Citation

> US National Institutes of Health, RePORTER application 10581244, Creation of a polygenic humanized mouse model for HIV-1 (3U42OD012210-23S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10581244. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*