Reduced cell size, chromosomal aberration and altered proliferation rates are characteristics and confounding factors in the STHdh cell model of Huntington disease

• Published in: Scientific reports Vol. 7; no. 1; pp. 16880 - 13
• Main Authors: Singer, Elisabeth, Walter, Carolin, Weber, Jonasz J., Krahl, Ann-Christin, Mau-Holzmann, Ulrike A., Rischert, Nadine, Riess, Olaf, Clemensson, Laura E., Nguyen, Huu P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.12.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 631/378/87; 631/80/103; 631/80/83; 692/699/375/1558; Animal models; Animals; Cell culture; Cell Line; Cell proliferation; Cell Proliferation - physiology; Cell Size; Cell Survival; Chromosome Aberrations; Confounding (Statistics); Data processing; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Embryos; Gene Knock-In Techniques; Humanities and Social Sciences; Huntingtin; Huntingtin Protein - genetics; Huntingtin Protein - metabolism; Huntington Disease - metabolism; Huntington Disease - pathology; Huntingtons disease; Mice; Models, Biological; multidisciplinary; Neostriatum; Neurodegenerative diseases; Polyglutamine; Science; Science (multidisciplinary); Trinucleotide repeat diseases; Trinucleotide repeats; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-17275-4

Huntington disease is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the gene encoding the huntingtin protein. Expression of the mutant protein disrupts various intracellular pathways and impairs overall cell function. In particular striatal neurons seem to be most vulnerable to mutant huntingtin-related changes. A well-known and commonly used model to study molecular aspects of Huntington disease are the striatum-derived ST Hdh cell lines generated from wild type and huntingtin knock-in mouse embryos. However, obvious morphological differences between wild type and mutant cell lines exist, which have rarely been described and might not have always been considered when designing experiments or interpreting results. Here, we demonstrate that ST Hdh cell lines display differences in cell size, proliferation rate and chromosomal content. While the chromosomal divergence is considered to be a result of the cells’ tumour characteristics, differences in size and proliferation, however, were confirmed in a second non-immortalized Huntington disease cell model. Importantly, our results further suggest that the reported phenotypes can confound other study outcomes and lead to false conclusions. Thus, careful experimental design and data analysis are advised when using these cell models.