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Development of an <i>in vivo</i>, screenable, split-luciferase based model of huntingtin multimerization.

Overview

Authors: Morgan G Thomas1, Simon A Levy2, Meredith H Jenkins1, Morgan Lambert1, Bess Frost1
ORCID iDs: Morgan G Thomas, Meredith H Jenkins, Bess Frost
  1. Center for Alzheimer’s Disease Research, Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA
  2. Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX, USA
Institutions: Brown University (United States); The University of Texas at San Antonio Health Science Center (United States)
Journal: iScience, volume 29, issue 7, article 116660
Dates: received 1 October 2025; accepted 17 June 2026; published online 7 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.116660 · PMID 42436982 · PMCID PMC13355796 · OpenAlex W7167605648
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: drosophila (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Huntington’s disease, huntingtin, polyglutamine, Drosophila, split-luciferase
Topic: Genetic Neurodegenerative Diseases (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institutes of Health (P40OD018537); NINDS NIH HHS (T32 NS082145); National Institute of Child Health and Human Development (IA 52242); NINDS (T32 NS082145); NIH HHS (P40 OD018537)
Citations: not cited yet (Europe PMC); 36 references in the paper
Research resources: Alexa Fluor 488 anti-rabbit RRID:AB_143165, Alexa Fluor 647 anti-mouse RRID:AB_2535804, Anti-mouse human ads-HRP RRID:AB_2619742, Huntingtin RRID:AB_2792860, Anti-rabbit human ads-HRP RRID:AB_2795919, Actin RRID:AB_528068, Lamin Dm0 RRID:AB_528338, pUA Plasmid RRID:Addgene_58372, W1118 RRID:BDSC_3605, Elav-Gal4 RRID:BDSC_458, GraphPad Prism RRID:SCR_002798

Abstract

Huntington’s disease is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in exon one of the gene that encodes for the protein huntingtin (HTT). PolyQ expansion drives HTT aggregation into multimeric species that range from soluble oligomers to fibrillar, insoluble inclusion bodies. Cellular mechanisms facilitating HTT aggregation are incompletely understood, hindering efforts to develop strategies that prevent inclusion body formation or promote clearance of misfolded protein. To enable future unbiased in vivo screening approaches to identify genetic modifiers and pharmacological strategies to suppress HTT aggregation, we have developed HTTLUM, a split-luciferase-based detector of HTT-HTT interaction in adult Drosophila melanogaster neurons. This system permits real-time monitoring of HTT multimerization in living, active flies. The non-lethal nature of the HTTLUM system enables subsequent analysis of HTT aggregation, neurotoxicity, and other phenotypes in the same flies, thus serving as a platform for medium-throughput screening followed by mechanistic validation of potential modifier candidates.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

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Data and code availability

All raw and processed data generated in this paper are available from the lead contact upon request.

This study does not report original code.

Any additional information required to reanalyze the data reported in this study is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 5 keywords, 5 funders, 36 references, 11 RRIDs.

Cite

This paper

Thomas, M. G., Levy, S. A., Jenkins, M. H., Lambert, M., & Frost, B. (2026). Development of an <i>in vivo</i>, screenable, split-luciferase based model of huntingtin multimerization. iScience, 29(7), 116660. https://doi.org/10.1016/j.isci.2026.116660

BibTeX

@article{thomas2026development,
author = {Thomas, Morgan G and Levy, Simon A and Jenkins, Meredith H and Lambert, Morgan and Frost, Bess},
title = {{Development of an \<i\>in vivo\</i\>, screenable, split-luciferase based model of huntingtin multimerization}},
journal = {iScience},
year = {2026},
month = jul,
volume = {29},
number = {7},
pages = {116660},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.116660},
url = {https://doi.org/10.1016/j.isci.2026.116660},
pmid = {42436982},
pmcid = {PMC13355796}
}

RIS

TY - JOUR
AU - Thomas, Morgan G
AU - Levy, Simon A
AU - Jenkins, Meredith H
AU - Lambert, Morgan
AU - Frost, Bess
TI - Development of an <i>in vivo</i>, screenable, split-luciferase based model of huntingtin multimerization
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/07/07
VL - 29
IS - 7
SP - 116660
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.116660
UR - https://doi.org/10.1016/j.isci.2026.116660
LA - en
ER -

CSL-JSON

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