Molecular features of a Huntington's disease knock-in minipig.
Overview
- Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov 27721, Czech Republic
- Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague 12800, Czech Republic
- Huntington's Disease Centre and Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
- Molecular Neurogenetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Neurology, Massachusetts Hospital and Harvard Medical School, Boston, MA 02114, USA
- CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation Inc., Princeton, NJ 08540, USA
Abstract
Huntington's disease is caused by a CAG expansion in the HTT gene, leading to somatic repeat instability, alternative processing of HTT pre-mRNA, and mutant huntingtin protein production. To model these features, we generated a knock-in minipig (KI-85Q-HD) carrying a (CAG)82CAA(CAG)2 repeat in the endogenous HTT locus. To evaluate this, we quantified somatic expansion in various tissues using small pool- and bulk-PCR; detected HTT1a, an aberrantly spliced HTT transcript, using 3′ rapid amplification of cDNA ends and quantitative PCR; and assessed mutant huntingtin protein isoforms using homogeneous time-resolved fluorescence assays. Moderate levels of tissue-specific and age-dependent somatic expansion were observed, highest in the caudate nucleus, kidney and spleen, and detectable in blood cells. We confirmed the presence of HTT1a transcripts terminating at a cryptic polyadenylation site in HTT intron 1, and detected soluble full-length mutant HTT and HTT1a proteins across brain regions and peripheral tissues, while aggregated HTT1a was only detected in the cortex. These results indicate that KI-85Q-HD minipigs exhibit molecular features of Huntington's disease at a pre-symptomatic stage and may serve as a platform for assessing therapeutic distribution and potency.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none, so it has no map.
Data
Datasets cited
- zenodo:17865624, at Zenodo; found in the text, “Footnotes”
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 21 authors, 5 keywords, 13 MeSH terms, 5 funders, 61 references.
Cite
This paper
Kolesnikova, A., Sathasivam, K., Tusi, S. K., Landles, C., Osborne, G. F., Kovalenko, M., Gillis, T., Kamenná, E., Sekáč, D., Nguyen, D. T., Valeková, I., Juhás, Š., Juhásová, J., Levinská, B., Baxa, M., Motlík, J., Klíma, J., Howland, D., Wheeler, V. C., . . . Ellederova, Z. (2026). Molecular features of a Huntington's disease knock-in minipig. Disease models & mechanisms, 19(5), dmm052803. https://
BibTeX
@article{kolesnikova2026
author = {Kolesnikova, Anastasiia and Sathasivam, Kirupa and Tusi, Solaleh Khoramian and Landles, Christian and Osborne, Georgina F and Kovalenko, Marina and Gillis, Tammy and Kamenná, Eva and Sekáč, David and Nguyen, Duong The and Valeková, Ivona and Juhás, Štefan and Juhásová, Jana and Levinská, Božena and Baxa, Monika and Motlík, Jan and Klíma, Jiří and Howland, David and Wheeler, Vanessa C and Bates, Gillian P and Ellederova, Zdenka},
title = {{Molecular features of a Huntington's disease knock-in minipig}},
journal = {Disease models \& mechanisms},
year = {2026},
month = may,
volume = {19},
number = {5},
pages = {dmm052803},
publisher = {Company of Biologists},
issn = {1754-8403},
doi = {10.1242/
url = {https://
pmid = {42186428},
pmcid = {PMC13267775}
}
RIS
TY - JOUR
AU - Kolesnikova, Anastasiia
AU - Sathasivam, Kirupa
AU - Tusi, Solaleh Khoramian
AU - Landles, Christian
AU - Osborne, Georgina F
AU - Kovalenko, Marina
AU - Gillis, Tammy
AU - Kamenná, Eva
AU - Sekáč, David
AU - Nguyen, Duong The
AU - Valeková, Ivona
AU - Juhás, Štefan
AU - Juhásová, Jana
AU - Levinská, Božena
AU - Baxa, Monika
AU - Motlík, Jan
AU - Klíma, Jiří
AU - Howland, David
AU - Wheeler, Vanessa C
AU - Bates, Gillian P
AU - Ellederova, Zdenka
TI - Molecular features of a Huntington's disease knock-in minipig
T2 - Disease models & mechanisms
J2 - Dis Model Mech
PY - 2026
DA - 2026/
VL - 19
IS - 5
SP - dmm052803
SN - 1754-8403
PB - Company of Biologists
DO - 10.1242/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1242/
"type": "article-journal",
"title": "Molecular features of a Huntington's disease knock-in minipig",
"container-title": "Disease models & mechanisms",
"author": [
{
"family": "Kolesnikova",
"given": "Anastasiia"
},
{
"family": "Sathasivam",
"given": "Kirupa"
},
{
"family": "Tusi",
"given": "Solaleh Khoramian"
},
{
"family": "Landles",
"given": "Christian"
},
{
"family": "Osborne",
"given": "Georgina F"
},
{
"family": "Kovalenko",
"given": "Marina"
},
{
"family": "Gillis",
"given": "Tammy"
},
{
"family": "Kamenná",
"given": "Eva"
},
{
"family": "Sekáč",
"given": "David"
},
{
"family": "Nguyen",
"given": "Duong The"
},
{
"family": "Valeková",
"given": "Ivona"
},
{
"family": "Juhás",
"given": "Štefan"
},
{
"family": "Juhásová",
"given": "Jana"
},
{
"family": "Levinská",
"given": "Božena"
},
{
"family": "Baxa",
"given": "Monika"
},
{
"family": "Motlík",
"given": "Jan"
},
{
"family": "Klíma",
"given": "Jiří"
},
{
"family": "Howland",
"given": "David"
},
{
"family": "Wheeler",
"given": "Vanessa C"
},
{
"family": "Bates",
"given": "Gillian P"
},
{
"family": "Ellederova",
"given": "Zdenka"
}
],
"container-title-short":
"volume": "19",
"issue": "5",
"page": "dmm052803",
"DOI": "10.1242/
"PMID": "42186428",
"PMCID": "PMC13267775",
"ISSN": "1754-8403",
"publisher": "Company of Biologists",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
5,
26
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1177/18796397261443137 [code]
- Towards AI-driven prediction of &
lt;i& gt;HTT& lt;/ i& gt; CAG size in super-expanded human spiny projection neurons from Huntington disease donors. Journal: Journal of Huntington's diseaseIn common: other condition, cellular / molecular, 9 references - [2] doi:10.1186/s13024-026-00960-2 [code]
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.Journal: Molecular neurodegenerationIn common: other condition, 6 references
- [3] doi:10.1242/dmm.052585
- Induced pluripotent stem cells from a transgenic minipig model of Huntington's disease reveal early metabolic changes.Journal: Disease models & mechanismsIn common: other, other condition, cellular / molecular, 1 reference, author Zdenka Ellederova
- [4] doi:10.1186/s13148-026-02082-4 [code]
- DNA methylation profiling in Huntington's disease reveals disease associated changes in the striatum.Journal: Clinical epigeneticsIn common: other condition, 5 references
- [5] doi:10.1016/j.mocell.2026.100363 [code]
- Tandem repeats in human brain evolution and disease susceptibility.Journal: Molecules and cellsIn common: cellular / molecular, 4 references
- [6] doi:10.1038/s41586-026-10671-9 [code]
- Restoring cortical disinhibition improves Huntington's disease phenotypes.Journal: NatureIn common: other condition, 4 references
- [7] doi:10.1038/s41586-026-10345-6 [code]
- Population-scale repeat expansions elucidate disease risk and brain atrophy.Journal: NatureIn common: other condition, 4 references
- [8] doi:10.1038/s41598-026-56101-8
- Topological modeling of gene expression in the brain with Huntington's disease reveals selective disruption of co-expression network.Journal: Scientific reportsIn common: other condition, cellular / molecular, 3 references
- [9] doi:10.1038/s44321-026-00459-9
- Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.Journal: EMBO molecular medicineIn common: other condition, cellular / molecular, 3 references
- [10] doi:10.1186/s10020-026-01471-y
- Modest rescue of RBFOX1 splicing function attenuates Huntington's disease features.Journal: Molecular medicine (Cambridge, Mass.)In common: other condition, 3 references
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.