Decreased synaptic ATP level in HD knock-in mouse brain. (A) Electron micrograph of EM48 immunogold labeling of the striatum of a 12-mo-old HD 150Q knock-in mouse brain. Arrows indicate degenerating mitochondria-like organelles. Double arrows indicate htt aggregates that were labeled by EM48 immunogold particles. Bar, 250 nm. (B) Western blotting of total cell lysates (T), cytoplasmic (C), synaptosomal (S), and nuclear (N) fractions isolated from the brain of wild-type (WT) and HD 150Q knock-in (KI) mice at 14 mo of age. The blots were probed with 1C2 for htt and antibodies to the mitochondrial protein SDH, the cytoplasmic protein GAPDH, the synaptic protein syntaxin, and the nuclear protein TBP. Arrow indicates full-length mutant htt. (C) Densitometry analysis of the ratio (mean + SEM, n = 3) of SDH to GAPDH or syntaxin. (D) ATP content (raw luminescence [A.U.]) in total cell lysates and synaptosomes isolated from the striatum of wild-type and HD KI mice at 12–14 mo of age. The data were presented as mean + SEM (n = 5–6). *, P < 0.05 as compared with wild type.