Brain, behavioral, and testis abnormalities of Ate1-deficient mice.

<p>(A) Enlarged brains of Ate1-deficient mice. Upper panel: comparison of representative brains harvested from an <i>Ate1^+/+</i> and an <i>Ate1^−/−</i> mouse, respectively, 134 days after tamoxifen (TM) treatment. Lower panel: brain weights expressed as percentages of total body weights in <i>Ate1^+/+</i> (n = 41) and <i>Ate1^−/−</i> (n = 40) mice. Horizontal bars and numbers indicate mean values. (B) Wet (0.4053 g versus 0.4608 g) and dry (0.1022 g versus 0.1119 g) weight components of the total mean brain weights (±SD) in <i>Ate1^+/+</i> and <i>Ate1^−/−</i> mice. (C) Total distance traveled (in meters), over 15 min, in an open field test among mice of different genotypes belonging to the same litter, 44 days after TM-treatment. Bar 1, <i>Ate1^flox/+</i>;<i>CaggCreER</i> mouse. Bar 2, <i>Ate1^+/+</i>;<i>CaggCreER</i> mouse. Bar 3, <i>Ate1^+/+</i> mouse. Bar 4, <i>Ate1^flox/−</i>;<i>CaggCreER</i> mouse that was converted to <i>Ate1^−/−</i> by TM treatment. Blue and red bars denote Ate1-containing and Ate1-deficient mice, respectively. (D) Same as in C but maximum lengths of single movements (in centimeters). (E) Same as in C but mean velocities (in cm/second) over 15 min. (F) Paraffin sections (4 µm) of testis showing cross-sections of seminiferous tubules in <i>Ate1^+/+</i> testis stained with hematoxylin and eosin (150× magnification). (G) Same as in F but <i>Ate1^−/−</i> testis. Note that sperm tails in the lumens of <i>Ate1^−/−</i> tubules are sparse in comparison to those in <i>Ate1^+/+</i> testis. (H) Same as in F but at 600× magnification. (I) Same as in G but at 600× magnification. (J) XGal staining for βgal activity in a 10-µm section of <i>Ate1^+/−</i> testis in which one copy of <i>Ate1</i> was replaced by an ORF encoding NLS-β-galactosidase and expressed from the P<i>_Ate1</i> promoter (100× magnification). (K) Immunoblotting analysis, using antibody to poly (ADP-ribose) polymerase (PARP), of testis extracts from an Ate1-containing (<i>Ate1^flox/−</i> (+/−)) and an Ate1-deficient (<i>Ate1^flox/−</i>;<i>CaggCreER</i> (−/−)) mouse 16 days after TM treatment. Note the loss of the full-length length 116 kDa PARP and the presence of the 85 kDa PARP fragment (lane2). An asterisk denotes a protein crossreacting with anti-PARP antibody.