# A murine model of Lyme neuroborreliosis

> **NIH NIH R21** · MICHIGAN STATE UNIVERSITY · 2024 · $187,734

## Abstract

PROJECT SUMMARY
Lyme disease (LD), the most prevalent tick-borne illness in the US (~300,000-475,000 annual cases), is
caused by spirochetes of Borreliella burgdorferi (Bb) sensu lato (s.l.) complex. When early LD diagnosis is
missed, it is left untreated and LD becomes chronic. Human vaccine is unavailable. Antimicrobial treatment of
chronic/persistent infection is often unrewarding. LD may last for years, presenting itself as skin lesions,
arthritis, carditis, and/or Lyme neuroborreliosis (LNB). Both central (CNS) and peripheral nervous systems
(PNS) are affected, which results in headache, fatigue, memory loss, depression, facial nerve palsy among
others. The main reason for incomplete understanding of LNB is the limited availability of adequate animal
models. Nonhuman primates are the only model that demonstrates similarities to clinical manifestations of
human LNB. However, issues of cost, reagents availability, non-reproducible genetic backgrounds, and ethical
concerns limit their use. Laboratory mouse strains do not develop neurological clinical signs and encephalitis.
The current knowledge gap is the lack of suitable mouse models of LNB. The overall objective is to develop
mouse model that will be permissive to Bb entry into the CNS/PNS, develop inflammatory lesions in the neural
tissues, and exhibit neurological signs. In the preliminary 3-year-long study, the Collaborative Cross (CC)
resource (32 lines; ~240 mice) was extensively used to identify the mouse model of LNB. The data showed
that 100% of mice of CC line E, which were infected with Bb for 6 months, including the mouse that exhibited
neurological signs upon Bb infection, developed significant inflammatory lesions in the brain, spinal cord,
and/or peripheral nerves. In this application, it is proposed to test different neurotropic Bb strains using CC line
E whose mice showed Bb infection-induced inflammation in their neural tissues upon Bb infection. It is also
proposed to include new 18 CC lines that have not been tested, so that a total of 50 CC lines (32+18) will be
used to identify genetic factors contributing to LNB via quantitative trait locus anlaysis. The following Specific
Aims will be pursued: SA1: Determine if line E mice infected with different neurotropic strains of Bb s.l.
will produce distinct LNB phenotypes; SA2: Localize genetic factors contributing to LNB.
This approach is innovative as the CC resource has never been utilized in the LD research field. Identifying a
single CC line that consistently shows the presence of inflammation and/or spirochetes in the neural tissues
will be considered a substantial advance in the field of LNB. The mapping resolution is expected to identify
causal regions with confidence, and the number, effect sizes, and relationship among QTL identified will help
guide subsequent investigations and provide the foundation for a future R01 application. The proposed
research is significant because a mouse model of LNB will allow the scienti...

## Key facts

- **NIH application ID:** 10786495
- **Project number:** 1R21AI180412-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Artem S Rogovsky
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,734
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786495

## Citation

> US National Institutes of Health, RePORTER application 10786495, A murine model of Lyme neuroborreliosis (1R21AI180412-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10786495. Licensed CC0.

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