Tg(C9orf72_i3)101Lutzy

The transgenic construct contains a bacterial artificial chromosome (BAC) clone derived from fibroblasts of a patient with amyotrophic lateral sclerosis (ALS), carrying the human chromosome 9 open reading frame 72 gene (C9orf72) with a hexanucleotide repeat expansion (GGGGCC) in the intron between the alternatively-spliced non-coding first exons 1a and 1b. Sequence isolated from the BAC included a ~166 kbp sequence (~36 kbp human C9orf72 genomic sequence, with ~110 kbp upstream and ~20 kbp downstream sequences). Upon amplification of different BAC subclones in bacteria, the repeat expansion underwent contraction in some clones. This BAC subclone is limited to a contraction of 100-750 GGGGCC repeats. At least 3 copies of the transgene integrated in tandem (segregating together); each copy harboring 780, 530 and 170 GGGGCC repeats, as determined by southern blot. (J:101977)