IngentaConnect Long glutamine tracts cause nuclear localization of a novel form ...

Authors: Wheeler, Vanessa C.¹; White, Jacqueline K.¹; Gutekunst, Claire-Anne²; Vrbanac, Vladimir¹; Weaver, Meredith¹; Li, Xiao-Jiang³; Li, Shi-Hua³; Yi, Hong²; Vonsattel, Jean-Paul⁴; Gusella, James F.¹; Hersch, Steven²; Auerbach, Wojtek⁵; Joyner, Alexandra L.⁵; MacDonald, Marcy E.¹

Source: Human Molecular Genetics, Volume 9, Number 4, 1 March 2000 , pp. 503-513(11)

Publisher: Oxford University Press

Abstract:

Huntington’s disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons. In precise genetic models of juvenile HD, Hdh^Q92 and Hdh^Q111 knock-in mice, long polyglutamine segments change huntingtin’s physical properties, producing HD-like in vivo correlates in the striatum, including nuclear localization of a version of the full-length protein predominant in medium spiny neurons, and subsequent formation of N-terminal inclusions and insoluble aggregate. These changes show glutamine length dependence and dominant inheritance with recruitment of wild-type protein, critical features of the altered HD property that strongly implicate them in the HD disease process and that suggest alternative pathogenic scenarios: the effect of the glutamine tract may act by altering interaction with a critical cellular constituent or by depleting a form of huntingtin essential to medium spiny striatal neurons.

Document Type: Research article

Affiliations: 1: Molecular Neurogenetics Unit, 2: Department of Neurology, 3: Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA, 4: Laboratory for Molecular Neuropathology Massachusetts General Hospital, Charlestown, MA 02129, USA, 5: Howard Hughes Medical Institute and Skirball Institute for Biomolecular Medicine and

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$48.69 plus tax Refund Policy

Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice

Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in Hdh^Q92 and Hdh^Q111 knock-in mice