Ablation of Arginylation in the Mouse N-End Rule Pathway: Loss of Fat, Higher Metabolic Rate, Damaged Spermatogenesis, and Neurological Perturbations
Figure 8
Brain abnormalities and behavioral phenotypes of Ate1-deficient mice.
(A) Ate1-deficient mice become hyperactive as a function of time after TM-mediated ablation of Ate1. Total distance (in cm) traveled over 15 min in the open field test box (2500 cm2). This test was repeated every ∼2 weeks after the end of TM treatment. The data for Ate1-containing mice (n = 5; their genotypes were Ate1flox/+, Ate1flox/−, and Ate1flox/+;CaggCreER) and Ate1-deficient mice (n = 3; Ate1flox/−;CaggCreER) are indicated by black diamonds and red circles, respectively. The horizontal bars indicate mean values. The average total distance traveled over 15 min for all Ate1-containing mice (n = 37) was 4,870 cm. (B) Representative magnetic resonance images showing equivalent horizontal planes of Ate1-containing (Ate1flox/+;CaggCreER on the left, Ate1flox/+ on the right) brains ∼3 months after TM treatment. The indicated average width of the skull (measured at the widest point from left to right in the same plane) of four Ate1-containing mice was 10.6 mm (±0.89 mm). (C) Same as in B except with brains from Ate1-deficient (Ate1flox/−;CaggCreER) mice ∼3 months after TM-treatment. The average width of the skull (measured as in B) of four Ate1-deficient mice was 10.8 mm (±0.38 mm). (D) Comparison of the response latency (Tmax; recorded in msec) between Ate1-containing (n = 3; black bars) and Ate1-deficient mice (n = 3; red bars) to a 40-msec pulse of 120 dB (p120; p<0.3), a 40-msec pulse of 120 dB preceded by a pre-pulse of 5 dB (pp5; p<0.09), or a 40-msec pulse of 120 dB preceded by a pre-pulse of 15 dB (pp15; p<0.01). Statistical analysis was performed using an unpaired t-test.