Upregulation of mbl Enhances Ataxin-3 Toxicity

Contact: Jordan Reese
jreese@upenn.edu
215-573-6604
University of Pennsylvania

Upregulation of mbl Enhances Ataxin-3 Toxicity

Caption: a–d, External (top) and internal (bottom) retinal cryosections of eyes of 1-day-old flies. a, Flies expressing gmr-GAL4 alone or b with mblB2–E1 have normal eye morphology. c, Flies expressing SCA3trQ61 have a mild loss of pigmentation, and slightly disrupted internal retinal morphology. d, Flies expressing SCA3trQ61 with mblB2–E1 show severe external degeneration and collapse of the retina. Genotypes w;gmr-GAL4 UAS-SCA3trQ61 in trans to c w or d mblB2–E1. Scale bar in d, 5 mum for retinal sections. e–h, Retinal pseudopupils of 1-day-old flies. e, Flies expressing elav-GAL4 alone or f with MblA have a normal pattern of seven photoreceptors per ommatidium. g, Flies expressing SCA3trQ78 show mild loss of retinal integrity (arrows), with 5.8 plusminus 0.4 s.d. photoreceptors per ommatidium (n = 200 ommatidia). Genotype elav-GAL4/+;UAS-SCA3trQ78/+. h, Co-expression of MblA with SCA3trQ78 enhances photoreceptor loss to 3.0 plusminus 0.5 s.d. (n = 200 ommatidia; significant difference from g, P < 0.0001 (two-tailed unpaired Student's t-test)). Genotype elav-GAL4/+;UAS-mblA/+;UAS-SCA3trQ78/+. i, Neuronal toxicity by lifespan analysis. Upregulation of MblA further shortened the lifespan of SCA3trQ78 flies, whereas downregulation of mbl (flies heterozygous for allele mblE27) extended lifespan (P < 0.001, SCA3trQ78 and SCA3trQ78/mblE27, SCA3trQ78 and SCA3trQ78/mblA, log-rank analysis). Mean plusminus s.d.; n = 170–220 flies for each genotype. Genotypes for SCA3trQ78 and SCA3trQ78/mblA are the same as g and h, SCA3trQ78/mblE27 is elav-GAL4/+;mblE27/+;UAS-SCA3trQ78/+.

Credit: Ling-Bo Li, Zhenming Yu, Xiuyin Teng & Nancy M. Bonini and the Journal, Nature

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