# Mouse models for study of the NLRP1 and CARD8 inflammasomes

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $233,250

## Abstract

ABSTRACT
 Inflammasomes are multiprotein complexes that function as cytosolic sensors. As such, they respond to
compromise and alteration of cellular metabolism and integrity resulting from both endogenous and exogenous
“danger-associated stimuli”. Conversely, aberrant and chronic inflammasome activation can contribute to
autoinflammatory diseases. Assembly of the inflammasome complex results in autoactivation of caspases,
maturation of IL-1β and IL-18, and often pyroptotic cell death. While there is a downstream commonality in the
events following inflammasome activation, the specificity of the response is dependent on germline-encoded
pattern recognition receptors triggered by the specific danger-associated stimuli. Many of the cellular sensors
such as NLRP3 belong to the NLR gene family, and much of our understanding of the contribution of individual
inflammasomes to the innate immune responses to a plethora of environmental challenges has been gleaned
from the study of mouse lines lacking various NLRs. In contrast, there is limited information regarding the
contribution to immune responses of two inflammasomes that are the focus of this proposal: NLRP1 and
CARD8. A major factor in the lack of information on these two related inflammasomes is the limited availability
of animal models to evaluate the function of the human inflammasome. Major differences in the functions of
human and mouse NLRP1 are suggested by species differences in NLRP1 protein structure and expression
pattern. In the case of CARD8, in vivo validation of the functions tentatively assigned to this protein have been
impossible in mice/rodents because the gene is absent in these species. Thus, the study of this inflammasome
has depended almost entirely on in vitro and ex vivo studies using human cell lines and tissue. We propose to
address this gap in our knowledge by utilizing syntenic replacement to generate novel mouse lines expressing
human NLRP1 and CARD8.

## Key facts

- **NIH application ID:** 10354472
- **Project number:** 1R21AI166471-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Beverly H Koller
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354472

## Citation

> US National Institutes of Health, RePORTER application 10354472, Mouse models for study of the NLRP1 and CARD8 inflammasomes (1R21AI166471-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10354472. Licensed CC0.

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