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. Author manuscript; available in PMC: 2016 Dec 2.
Published in final edited form as: Neuron. 2015 Dec 2;88(5):892–901. doi: 10.1016/j.neuron.2015.10.027

Figure 2. C9-BAC transgenic mice develop RNA foci and RAN peptides similar to human C9orf72 expansion carriers.

Figure 2

(A) Fluorescence in situ hybridization (FISH) of sense and antisense RNA foci in F08-CTR (red box) and F112 C9-BAC mice. CER-GL: cerebellar granular layer; CER-PC: cerebellar purkinje cells, hippo-DG: hippocampus dentate gyrus; FC: frontal cortex; PMC: primary motor cortex; SC-MN: spinal cord motor neuron. Scale bar = 10μm.

(B) Quantification of sense and antisense foci in nontransgenic (NTg), F08-CTR and F112 C9-BACexp transgenic mice across brain regions. Lower graph shows the percent of cells with foci across different brain regions at 3, 6, and 8 months of age.

(C) Immunostaining of poly(GP) in 20 month old NTg or F112 C9-BACexp mice showing inclusions in brain regions including cortex, hippocampus dentate gyrus (Hippo-DG), and cerebellar granular layer.

(D) Soluble poly(GP) is present in the cortex of 6 month-old C9-BACexp transgenic mice (F112 and F113), but not in NTg mice, nor F08-CTR mice, as assessed using a poly(GP) immunoassay. (n=2 for F112, F113, NTG, and F08-CTR)

(E) Insoluble poly(GP) levels are lower than soluble poly(GP) levels (C) in the cortex of C9-BACexp transgenic mice, as determined by immunoassay of the insoluble fraction. (n=2 for F112, F113, NTG, and F08-CTR)

(F) Immunoassay of Poly(GP) levels in different brain regions. Cerebellum showed the highest levels, while levels were lowest in the spinal cord. (n=3)

(G) Comparison of poly(GP) levels in the cortex from C9-BAC mouse lines and C9orf72-positive FTLD cases. Lines F112 and F113 produce poly(GP) at similar levels to those detected in two different human C9orf72+ FTD frontal cortex samples (FTD #1 and FTD #2). *All data are shown as mean ± SEM. See also Figure S2.