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Beschreibung

Protein C9orf72 (UniProt: Q96LT7) is encoded by the C9orf72 gene (Gene ID: 203228) in human. Expansion of a GGGGCC (G4C2) hexanucleotide repeat sequence in the non-coding region of human chromosome 9 open reading frame 72 or C9orf72 is the most common genetic abnormality in familial and sporadic frontotemporal dementia (FTD) and motor neuron disease (MND), with amyotrophic lateral sclerosis (ALS) as the most frequent form. The majority of normal human C9orf72 alleles carry less than 20 repeats, whereas large expansions consisting of hundreds or thousands of repeats lead to disease. C9orf72 generates three transcripts through alternative splicing that encode 2 protein isoforms, a long isoform of about 54 kDa (termed C9-L), corresponding to variants 2 and 3, and a short isoform of about 24 kDa (termed C9-S) corresponding to variant 1. Both isoforms are widely expressed, including kidney, lung, liver, heart, testis and several brain regions, including cerebellum, and frontal cortex. Both, C9-L and C9-S are reported to display distinct subcellular localizations in cerebellar Purkinje cells of both c9-ALS and nonc9-ALS cases. C9-L is shown to be spread diffusely throughout the cytoplasm, whereas C9- S is localized to the nuclear membrane of Purkinje cells of both c9-ALS and non-c9-ALS cases. Also, C9-L is shown to be present mainly in the high-salt Triton and urea-soluble fractions, whereas C9-S is shown to be abundant in both the low- and high-salt Triton fractions, indicating differences in their subcellular localizations. Antibodies generated against C9-L and C9-S offer advantage because they allow characterization of different biochemical profiles, region-specific changes, and subcellular localizations that is not possible with antibodies generated against the common N-terminal region.