Brain abnormalities and behavioral phenotypes of Ate1-deficient mice.

<p>(A) Ate1-deficient mice become hyperactive as a function of time after TM-mediated ablation of <i>Ate1</i>. 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 <i>Ate1^flox/+</i>, <i>Ate1^flox/−</i>, and <i>Ate1^flox/+</i>;<i>CaggCreER</i>) and Ate1-deficient mice (n = 3; <i>Ate1^flox/−</i>;<i>CaggCreER</i>) 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 (<i>Ate1^flox/+</i>;<i>CaggCreER</i> on the left, <i>Ate1^flox/+</i> 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 (<i>Ate1^flox/−</i>;<i>CaggCreER</i>) 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 (T_max; 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.