Huntingtin (UniProt P42858; also known as HD protein, Huntington disease protein) is encoded by the HTT (also known as HD, IT15) gene (Gene ID 3064) in human. Misfolding and self-aggregation of specific proteins are a common feature of well known neurodegenerative diseases, including Huntington s disease (HD), Alzheimer s disease (AD), Parkinson s disease (PD), and amyotrophic lateral sclerosis (AML). Abnormal polyglutamine (polyQ) repeat sequence or stretch result in protein misfolding and neurodegeneration. HD, for example, is caused by polyQ expansion in the first exon-coded sequence of the causal protein Huntingtin (Htt exon 1). The expanded polyQ leads to formation of beta-sheet rich fibrillar aggregates called amyloid. Eight proteins containing polyQ tracts, but otherwise unrelated to htt, also result in protein misfolding and neurodegeneration upon polyQ expansion. Growing evidences implicate soluble oligomers or even monomers of disease-causing amyloid proteins as the more toxic species. In HD, formation of the end-stage, very large aggregated species of mutant htt (mHtt), termed an inclusion bodies (IBs), is believed to be a coping response to sequester toxic species of monomeric or small oligomeric mHtt, which are distributed diffusely throughout the neuron.
Synonyms: Huntingtin mutants with expanded polyQ repeats, HD protein, Huntington disease protein, mHtt, PolyQ disease proteins
Application: Electron Microscopy Analysis: A representative lot immunostained transiently expressed Huntington (Htt) N-terminal fragment with 97 polyQ expansions in transfected neurons. Clone 3B5H10 labeled diffuse Htt in the cytoplasm with little staining of Htt in organelles and no staining of Htt in large inclusion bodies (IBs) (Miller, J., et al. (2011). Nat. Chem. Biol. 7(12):925-934).Immunocytochemistry Analysis: A representative lot immunostained neurons transiently expressing Huntington (Htt) or Ataxin-3 with disease-associated polyQ expansions (Q46 to Q138), but not neurons expressing Htt with Q17 or Ataxin-3 with Q27. Clone 3B5H10 stained diffuse mutant Htt (mHtt), but not aggregated Htt in large inclusion bodies (IBs) (Miller, J., et al. (2011). Nat. Chem. Biol. 7(12):925-934).Immunohistochemistry Analysis: A representative lot immunostained brain tissue sections from transgenic mice expressing disease-associated human mutant Huntinton (mHtt) proteins, including murine strains BACHD (full-length mHtt with Q97), R6/2 (Exon 1 fragment with ~Q150), and YAC-SCA3 (full-length mHtt with Q84). Clone 3B5H10 stained diffuse mHtt and failed to stain tissue with extensively aggregated Htt unless strong antigen retrieval by 90% formic acid treatment was performed (Miller, J., et al. (2011). Nat. Chem. Biol. 7(12):925-934).Inhibition Analysis: A representative lot prevented the aggregation of mutant Htt (mHtt) exon 1 fragment with Q39 or Q53 and disrupted pre-aggregated mHtt oligomers and fibrils into monomer in vitro by atomic force microscopy (AFM) and dynamic light scattering (DLS) measurement (Miller, J., et al. (2011). Nat. Chem. Biol. 7(12):925-934).Western Blotting Analysis: A representative lot detected Huntington (Htt), androgen receptor (AR), and atrophin constructs with disease-associated polyQ expansions (Q65 to Q103), but not constructs with Q19 or Q25, exogenously expressed in HEK293 and PC12 cells. Clone 3B5H10 detected monomeric and possibly small oligomeric mHtt N-terminal fragments, but not large oligomers or high molecular weight aggregates (Miller, J., et al. (2011). Nat. Chem. Biol. 7(12):925-934).
Other Notes: Concentration: Please refer to lot specific datasheet.