# Developing a murine TPI Df model

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $157,750

## Abstract

Abstract/Project summary:
TPI Df is a devastating untreatable childhood metabolic disease resulting in anemia,
paralysis, irreversible brain damage and premature death. Numerous subtle amino acid
substitutions in Triosephosphate Isomerase (TPI) are pathogenic and result in rapidly
progressing multisystem disease. Importantly, pathogenic TPI Df mutations have been
shown to result in protein that retains function but are unstable. Pathogenesis of numerous
TPI DF mutations is known to result from increased turnover of the functioning protein by
Protein Quality Control pathways (PQC). We have developed a human cellular TPI Df
model of the “common” mutation and validated its use in optical screening. We are utilizing
this model in an automated compound screening platform to identify first in class TPI Df
small molecule therapies. To validate small molecule therapies there is a desperate need
for a mammalian model of TPI Df. This proposed research will meet this need by using
CRISPR to create a TPI Df model with the “common” mutation. A mouse model with
construct validity for TPI Df that demonstrates analogous behavioral, physiological, and
metabolic phenotypes is an important resource for the research community.

## Key facts

- **NIH application ID:** 10294798
- **Project number:** 1R03NS119664-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Michael John Palladino
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,750
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294798

## Citation

> US National Institutes of Health, RePORTER application 10294798, Developing a murine TPI Df model (1R03NS119664-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294798. Licensed CC0.

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