@article{c79cd6a918894d0ca1afd8444e3bcfb8,
title = "Plasma PolyQ-ATXN3 Levels Associate With Cerebellar Degeneration and Behavioral Abnormalities in a New AAV-Based SCA3 Mouse Model",
abstract = "Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited cerebellar ataxia caused by the expansion of a polyglutamine (polyQ) repeat in the gene encoding ATXN3. The polyQ expansion induces protein inclusion formation in the neurons of patients and results in neuronal degeneration in the cerebellum and other brain regions. We used adeno-associated virus (AAV) technology to develop a new mouse model of SCA3 that recapitulates several features of the human disease, including locomotor defects, cerebellar-specific neuronal loss, polyQ-expanded ATXN3 inclusions, and TDP-43 pathology. We also found that neurofilament light is elevated in the cerebrospinal fluid (CSF) of the SCA3 animals, and the expanded polyQ-ATXN3 protein can be detected in the plasma. Interestingly, the levels of polyQ-ATXN3 in plasma correlated with measures of cerebellar degeneration and locomotor deficits in 6-month-old SCA3 mice, supporting the hypothesis that this factor could act as a biomarker for SCA3.",
keywords = "ATXN3, Machado-Joseph disease, SCA3, aav, biomarker, mouse model, polyglutamine, spinocerebellar ataxia 3",
author = "Karen Jansen-West and Todd, {Tiffany W.} and Daughrity, {Lillian M.} and Mei Yue and Jimei Tong and Yari Carlomagno and {Del Rosso}, Giulia and Aishe Kurti and Jones, {Caroline Y.} and Dunmore, {Judith A.} and Monica Castanedes-Casey and Dickson, {Dennis W.} and Wszolek, {Zbigniew K.} and Fryer, {John D.} and Leonard Petrucelli and Mercedes Prudencio",
note = "Funding Information: This work was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (R35NS097273 (LP), U54NS123743 (LP, MP), P01NS084974 (LP), RF1NS120992 (MP)), the Mayo Clinic Foundation (LP), and the Donald G. and Jodi P. Heeringa Family (ZW, LP). ZW is partially supported by the National Institutes of Health/National Institute of Aging and National Institute of Neurological Disorders and Stroke (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, a gift from The Sol Goldman Charitable Trust, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson{\textquoteright}s Research Foundation. Publisher Copyright: Copyright {\textcopyright} 2022 Jansen-West, Todd, Daughrity, Yue, Tong, Carlomagno, Del Rosso, Kurti, Jones, Dunmore, Castanedes-Casey, Dickson, Wszolek, Fryer, Petrucelli and Prudencio.",
year = "2022",
month = mar,
day = "21",
doi = "10.3389/fcell.2022.863089",
language = "English (US)",
volume = "10",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media S. A.",
}