Figure 1. Genetic interactions of
pgrn-1 in disease models:The genetic loss of
pgrn-1 exacerbates the paralysis phenotypes of TDP-43A315T (A, p=0.0041) and FUS
x2206;S57 (B, p=0.0007) transgenic animals, and of
ptl-1(
ok621) (D, p<0.0001),
cdc-48.1(
tm544) (E, p=0.0016), and
sqst-1(
ok2892) (F, p<0.0001) mutant animals. Paralysis of
alfa-1(
ok3062) animals are not affected by the loss of
pgrn-1 (C, n.s.), and neither are
ubql-1(
ok997) (G, n.s.) and
smn-1(
gk118916) (I, n.s.) animals after depletion of
pgrn-1 by RNAi. RNAi experiments were conducted in the uIs60 [
unc-119p::YFP +
unc-119p::
sid-1] background. (A-F, H, J) The overexpression of full-length, wild-type PGRN-1 ameliorates paralysis in all disease models tested (A, p=0.0003; B, p=0.0015; C, p<0.0001; D, p=0.0006; E, p=0.0232; F, p<0.0001; H, p=0.0011; J, p<0.0001). Data on graphs are presented as mean +/- SEM, gathered from multiple biological replicates. (PGRN-1 O/E=PGRN-1 overexpressing strain; black numbers= total worm population; blue numbers= paralyzed animals; red numbers= censored animals)