Characterization of Huntingtin Pathologic Fragments in Human Huntington Disease, Transgenic Mice, and Cell Models

• DOI: 10.1097/nen.0b013e318040b2c8
• Publication Date: 2008-05-04T12:49:38Z
• Authors: Gabriele Schilling; Alexandra Klevytska; Andrew T. N. Tebb...; Katrin Juenemann; Jillian Cooper; Victoria Gonzales; Hilda Slunt; Michelle Poirer; Christopher A. Ross; David R. Borchelt
• Keywords: Huntingtin Protein

Huntington disease (HD) is caused by the expansion of a glutamine (Q) repeat near N terminus huntingtin (htt), resulting in altered conformation mutant protein to produce, most prominently brain neurons, nuclear and cytoplasmic inclusion pathology. The inclusions associated diffuse accumulation htt nuclei are composed N-terminal fragments protein. Here, we used panel peptide antibodies characterize pathologies tissues from human HD, transgenic mouse model created expressing first 171 amino acids with 82Q (htt-N171-82Q). In both sources, pathologic features were detected peptides 1-17 81-90 but not 115-129 (wild-type numbering 23 repeats). Human HEK 293 cells transfected expression vectors that encode either 233 (htt-N233-82Q) or htt-N171-18Q accumulated smaller antibody-binding characteristics identical those peptides. We conclude accumulate structures HD httN171-82Q mice produced similar, yet be defined, proteolytic events region within 90-115.