# ANO5 in Muscle Health and Disease

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $624,760

## Abstract

PROJECT SUMMARY
Mutations in ANO5 have been linked to several human diseases including muscular dystrophy. Ano5 is an
intracellular membrane protein, belonging to the anoctamin protein family. Many of the proteins in this family
have been found to possess the Ca2+-activated phospholipid scrambling activity. Despite the clear genetic
linkage between ANO5 and muscular dystrophy in patients, we found that complete KO of Ano5 in mice
showed no overt muscle pathology during our last funding period. This was independently confirmed by other
investigators using a different line of complete Ano5-KO mice. These findings indicate that a potential
compensatory mechanism, likely through other anoctamin proteins, is involved in minimizing the impact of
complete Ano5 deficiency. Intriguingly, an Ano5-KO mouse expressing putatively a truncated Ano5 peptide
developed clinical signs of muscular dystrophy with intracellular aggregates and defective membrane repair.
Many of the ANO5 mutations associated with human muscular dystrophy are premature termination mutations.
These findings raise an interesting question about how ANO5 mutations cause muscle degeneration in human
patients: does the expression of mutant amino-terminal Ano5 peptide lead to muscular dystrophy by promoting
the formation of intracellular aggregates and compromising membrane repair machinery? Our continuing
research in this proposal is centered on determining the fundamental role of the amino-terminus of Ano5 in
regulating the intrinsic lipid scrambling function of anoctamins proteins, membrane repair and its contribution to
the pathogenesis of muscular dystrophy caused by ANO5 mutations. Moreover, our studies will reveal the
compensatory mechanism underlying the lack of muscular dystrophy phenotype in complete Ano5-KO mice.
Through the use of in vivo CRISPR gene editing, biochemical, histopathological, and living cell imaging studies
with animal models, our planned experiments shall advance our understanding of the physiological and
pathological roles of amino-terminal Ano5 peptides in muscle and also shed critical insights into the
development of novel therapeutic strategies for the treatment of Ano5-related muscular dystrophy.

## Key facts

- **NIH application ID:** 9859226
- **Project number:** 5R01HL116546-08
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Renzhi Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $624,760
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859226

## Citation

> US National Institutes of Health, RePORTER application 9859226, ANO5 in Muscle Health and Disease (5R01HL116546-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859226. Licensed CC0.

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