Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis

• DOI: 10.1371/journal.pgen.1006846
• Publication Date: 2017-07-17T17:35:33Z
• Authors: Paula Dietrich; Irudayam Maria Jo...; Shanta Alli; Ioannis Dragatsis
• Keywords: Huntingtin Protein; Neuropathology; Polyglutamine tract

Huntington's Disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by cognitive, behavioral and motor dysfunctions. HD caused a CAG repeat expansion in exon 1 of the gene that translated into expanded polyglutamine tract encoded protein, huntingtin (HTT). While most significant neuropathology occurs striatum, other brain regions are also affected play important role pathology. To date there no cure for HD, recently strategies aiming at silencing HTT expression have been initiated as possible therapeutics HD. However, essential functions adult currently unknown hence consequence sustained suppression unpredictable can potentially be deleterious. Using Cre-loxP system recombination, we conditionally inactivated mouse homologue 3, 6 9 months age. Here show elimination Htt results deficits, neuropathological changes including bilateral thalamic calcification, altered iron homeostasis.