Molecular characterisation and somatic instability in the F344tgHD rat model of Huntingtons disease [Conference Abstract]

Fears, Kyle, Durairaj, Ruban Rex, Edwards, Olivia, Randall, Emma, Aston, Alys, Bhattacharyya, Soumyasree, Baptiste, Rashida, Lelos, Mariah ORCID: https://orcid.org/0000-0001-7102-055X and Dion, Vincent ORCID: https://orcid.org/0000-0003-4953-7637 2026. Molecular characterisation and somatic instability in the F344tgHD rat model of Huntingtons disease [Conference Abstract]. Journal of Neurology, Neurosurgery and Psychiatry 97 (Supp 2) , pp. A23-A24. 10.1136/jnnp-2026-ehdn.58

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Abstract

Background: The F344tgHD transgenic rat model of Huntington’s disease (HD) has undergone extensive phenotypic characterisation, displaying progressive HD-like behavioural and neuropathological changes despite carrying only 51 CAG repeats within a randomly inserted chimeric transgene. However, the structure of the transgene insertion has not been characterised, nor has somatic instability been quantified in this model. Aims: We aimed to locate the transgene insertion site(s), determine transgene copy number and orientation, and quantify tissue-specific somatic expansion in brain and peripheral tissues. Methods/Techniques: The transgene insertion site was located and initial copy number imputed using next-generation whole genome sequencing and downstream bioinformatic analysis. Tissue-specific somatic expansion was assessed using PacBio amplicon sequencing and small-pool PCR. Results/Outcome: Multiple copies of the transgene were found to be inserted at a single site immediately upstream of the endogenous rat Htt locus on chromosome 14, a configuration consistent with integration by homologous recombination. Despite carrying a CAG repeat length within the adult-onset human pathogenic range, the model also displayed tissue-specific somatic expansion at advanced ages, with more pronounced expansion in striatum and liver. Conclusions: The F344tgHD rat carries a tandem transgene array at a single insertion site on chromosome 14, and exhibits a tissue-specific pattern of somatic expansion mirroring that seen in patients and in HD rodent models carrying substantially longer CAG repeats. These findings, in addition to previous behavioural characterisations, position the F344tgHD rat as an attractive in vivo model for therapeutic development and testing in the context of human HD-relevant CAG repeat lengths.

Item Type:	Short Communication
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Schools > Biosciences
Publisher:	BMJ Publishing Group
ISSN:	0022-3050
Last Modified:	28 Oct 2026 12:46
URI:	https://orca.cardiff.ac.uk/id/eprint/190499

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