Figure 7.

C9orf72 repeat instability, chromosomal fragility and chromosomal instability in C9orf72Exp-Tg-mice. Southern blots for C9orf72 transgene in C9-500 mouse tissues. C9-500 mouse tissues were sized for repeat size via Southern blot in three C9orf72Exp Tg-mice. The tail was the most stable tissue. (A) Somatic repeat instability by Southern blots in tissues of three 5-month-old C9orf72Exp-Transgenic mice harboring a single copy of the human C9orf72 gene with a GGGGCC expansion integrated into murine Chr6 (156). (B) Cells isolated from tissues of the mice shown in panel (A) were grown for 1–4 weeks sufficient for metaphase spreads for fragility analysis with 1 μM FUdR with FISH analysis. A murine-specific green probe identified mouse Chr6, and human-specific red probe identified the C9orf72Exp transgene. Pictured are FSFS in the CNS (i), the periphery (ii) and quantified in panel (iii). (C) Chromosomal instability at the C9orf72Exp transgene was assessed in the same tissues used in panel (C), using the same FISH probes.