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. 2018 May 10;11:27. doi: 10.1186/s13041-018-0370-y

Table 1.

Phenotype of Rapgef2-cKO and Rapgef6-KO mice in comprehensive behavioral test battery

Task Test Measure Rapgef2-cKO Rapgef6-KO Statistical analysis Figure
(vs. Non-cKO) (vs. WT) Rapgef2-cKO Rapgef6-KO
Physical characteristics Body weight Weight (g) n.s. – – F1,43 = 1.745, p = 0.1935 F1,38 = 12.541, p = 0.0011 Fig. 1a, e
Body temperature Temperature (°C) n.s. n.s. F1,43 = 1.991, p = 0.1654 F1,38 = 4.036, p = 0.0517 Fig. 1b, f
Grip strength (N) Strength (N) n.s. n.s. F1,43 = 1.149, p = 0.2897 F1,38 = 0.062, p = 0.8053 Fig. 1c, g
Wire hang latency (s) Latency (s) – – n.s. F1,43 = 16.785, p = 0.0002 F1,38 = 0.04, p = 0.8425 Fig. 1d, h
Motor coordination Rotarod Latency to fall (s) n.s. n.s. F1,43 = 1.251, p = 0.2695 F1,38 = 0.708, p = 0.4052 Fig. 1i, j
Pain sensitivity Hot plate Latency (s) – n.s. F1,43 = 5.043, p = 0.0299 F1,38 = 1.045, p = 0.3131 Fig. 1k, l
Exploratory locomotion Open field test Distance traveled (cm) + + + + (initial phase) F1,43 = 36.348, p < 0.0001 F1,38 = 0.03, p = 0.8638 Fig. 2a, c
Anxiety-like behavior Open field test Center time (s) + + + + (initial phase) F1,43 = 19.658, p < 0.0001 F1,38 = 0.002, p = 0.9656 Fig. 2b, d
Light/dark transition test Number of transitions n.s. n.s. F1,43 = 0.735, p = 0.3961 F1,38 = 0.395, p = 0.5335 Fig. 2e, g
Latency to light chamber (s) n.s. n.s. F1,43 = 0.501, p = 0.4827 F1,38 = 0.669, p = 0.4187 Fig. 2f, h
Elevated plus maze test Entries into open arms (%) + + n.s. F1,42 = 8.453, p = 0.0058 F1,38 = 1.328, p = 0.2564 Fig. 2i, k
Time on open arms (%) + n.s. F1,42 = 6.229, p = 0.0166 F1,38 = 0.095, p = 0.7597 Fig. 2j, l
Behavioral despair Porsolt forced swim test Immobility (%) on Day 1 n.s. - (1-7 min) F1,43 = 2.71, p = 0.107 F1,38 = 1.881, p = 0.1783;
1-7 min, F1,38 = 5.089, p = 0.0299		 Fig. 3a, b
Immobility (%) on Day 2 - (1-3 min),
+ + (4-10 min)		 - (1-2 min) F1,43 = 0.065, p = 0.8007;
1-3 min, F1,43 = 6.82, p = 0.0124;
4-10 min, F1,43 = 17.252, p = 0.0002		 F1,38 = 2.952, p = 0.0939;
1-2 min, F1,38 = 4.865, p = 0.0335		 Fig. 3a, b
Tail suspension test Immobility (%) + + (7-10 min) n.s. F1,43 = 3.569, p = 0.0656;
7-10 min, F1,43 = 8.574, p = 0.0054		 F1,38 = 2.651, p = 0.1118 Fig. 3c, d
Sensorimotor gating Startle response test Startle response – – F1,43 = 4.129, p = 0.0484 F1,38 = 6.287, p = 0.0166 Fig. 4a, c
Prepulse inhibition test PPI (startle stimulus, 110 dB) n.s. n.s. F1,43 = 1.161, p = 0.2873 F1,38 = 1.007, p = 0.322 Fig. 4b, d
PPI (startle stimulus, 120 dB) n.s. n.s. F1,43 = 0.293, p = 0.5912 F1,38 = 0.222, p = 0.6404 Fig. 4b, d
Social interaction Novel environment Total duration of contacts (s) n.s. n.s. F1,18 = 0.048, p = 0.8299 F1,18 = 0.215, p = 0.6484 Fig. 5a, f
Number of contacts + + + + + F1,18 = 28.989, p < 0.0001 F1,18 = 9.088, p = 0.0074 Fig. 5b, g
Total duration of active contacts (s) + + + n.s. F1,18 = 27.519, p < 0.0001 F1,18 = 4.132, p = 0.0571 Fig. 5c, h
Mean duration of contact (s) – – F1,18 = 5.566, p = 0.0298 F1,18 = 5.719, p = 0.0279 Fig. 5d, i
Distance traveled (cm) + + + + F1,18 = 39.017, p < 0.0001 F1,18 = 6.421, p = 0.0208 Fig. 5e, j
Home cage Mean number of particles n.s. n.s. F1,16 = 0.743, p = 0.4016;
light period, F1,16 = 0.031, p = 0.8628;
dark period, F1,16 = 1.65, p = 0.2173		 F1,18 = 0.002, p = 0.9695;
light period, F1,18 = 0.438, p = 0.5163;
dark period, F1,18 = 0.143, p = 0.7097		 Fig. 5k, m
Activity levels n.s. n.s. F1,16 = 0.141, p = 0.712;
light period, F1,16 = 0.928, p = 0.3497;
dark period, F1,16 = 0.546, p = 0.4705		 F1,18 = 0.031, p = 0.8633;
light period, F1,18 = 0.96, p = 0.3401;
dark period, F1,18 = 0.169, p = 0.6858		 Fig. 5l, n
Crawley’s version Time spent around cage (s) on 1st – – n.s. F1,43 = 8.754, p = 0.005 F1,38 = 1.221, p = 0.276 Fig. 5o, p
Time spent around cage (s) on 2nd – – n.s. F1,43 = 9.539, p = 0.0035 F1,38 = 0.014, p = 0.9074 Fig. 5o, p
Spatial memory Barnes maze test
Acquisition test Latency to 1st (s) n.s. n.s. F1,43 = 2.556, p = 0.1172 F1,38 = 0.0004, p = 0.9841 Fig. 6a, n
Error to 1st + + + n.s. F1,43 = 18.985, p < 0.0001 F1,38 = 0.657, p = 0.4228 Fig. 6b, o
Distance to 1st (mm) + + + n.s. F1,43 = 18.746, p < 0.0001 F1,38 = 0.668, p = 0.4187 Fig. 6c, p
Probe test (1-day after training) Latency to 1st (s) + + n.s. F1,43 = 8.983, p = 0.0045 F1,38 = 1.506, p = 0.2273 Fig. 6d, q
Error to 1st + + n.s. F1,43 = 13.605, p = 0.0006 F1,38 = 0.463, p = 0.5005 Fig. 6e, r
Distance to 1st (mm) + + n.s. F1,43 = 16.909, p = 0.0002 F1,38 = 0.544, p = 0.4653 Fig. 6f, s
Time spent around each hole (s) n.s. n.s. F1,43 = 0.062, p = 0.8026 F1,38 = 0.35, p = 0.5576 Fig. 6g, t
Time spent around target hole (s) – – – n.s. F1,43 = 23.594, p < 0.0001 F1,38 = 0.3912, p = 0.0552 Fig. 6h, u
Probe test (1-month after training) Latency to 1st (s) n.s. n.s. F1,42 = 0.488, p = 0.4885 F1,38 = 1.705, p = 0.1995 Fig. 6i, v
Error to 1st + + n.s. F1,42 = 9.308, p = 0.0039 F1,38 = 2.786, p = 0.1033 Fig. 6j, w
Distance to 1st (mm) + n.s. F1,42 = 5.991, p = 0.0186 F1,38 = 4.029, p = 0.0519 Fig. 6k, x
Time spent around each hole (s) n.s. n.s. F1,42 = 6.468, p = 0.0148 F1,38 = 0.021, p = 0.886 Fig. 6l, y
Time spent around target hole (s) n.s. n.s. F1,43 = 0.317, p = 0.5762 F1,38 = 1.853, p = 0.1814 Fig. 6m, z
Working memory T-maze test Correct responses (%) – – – - - (delayed alternation) F1,43 = 30.696, p < 0.0001 Session 1-4, F1,38 = 1.361, p = 0.2506
Session 5-8, F1,38 = 7.996, p = 0.0074		 Fig. 7a, c
Cued and contextual fear conditioning Fear conditioning test
Conditioning Freezing (%) – – – – – F1,43 = 32.949, p < 0.0001 F1,38 = 10.046, p = 0.003 Fig. 8a, g
Context test 1 day after conditioning Freezing (%) – – – – F1,43 = 36.049, p < 0.0001 F1,38 = 6.837, p = 0.0127 Fig. 8b, h
Cued test 1 day after conditioning (pre-CS) Freezing (%) – – – F1,43 = 4.641, p = 0.0369 F1,38 = 10.947, p = 0.0021 Fig. 8b, h
Cued test 1 day after conditioning (CS) Freezing (%) n.s. – F1,43 = 4.003, p = 0.0517 F1,38 = 5.287, p = 0.0271 Fig. 8b, h
Context test 1 month after conditioning Freezing (%) – – – – F1,42 = 36.559, p < 0.0001 F1,38 = 4.772, p = 0.0352 Fig. 8c, i
Cued test 1 month after conditioning (pre-CS) Freezing (%) – – – F1,41 = 6.521, p = 0.0145 F1,38 = 15.314, p = 0.0004 Fig. 8c, i
Cued test 1 month after conditioning (CS) Freezing (%) – – F1,41 = 5.188, p = 0.028 F1,38 = 5.254, p = 0.0275 Fig. 8c, i
Fear conditioning test (foot shock 1) Distance traveled (cm) n.s. + + F1,43 = 10.489, p = 0.4883 F1,38 = 12.428, p = 0.0011 Fig. 8d, j
Fear conditioning test (foot shock 2) Distance traveled (cm) n.s. n.s. F1,43 = 0.423, p = 0.5189 F1,38 = 0.347, p = 0.5592 Fig. 8d, j
Fear conditioning test (foot shock 3) Distance traveled (cm) n.s. n.s. F1,43 = 1.026, p = 0.3168 F1,38 = 1.858, p = 0.1809 Fig. 8d, j
Context test 1 day after conditioning Activity suppression ratio + + n.s. F1,43 = 15.048, p = 0.0004 F1,38 = 1.699, p = 0.2002 Fig. 8e, k
Context test 1 month after conditioning Activity suppression ratio + + + n.s. F1,42 = 46.445, p < 0.0001 F1,38 = 0.154, p = 0.697 Fig. 8e, k
Cued test 1 day after conditioning (CS) Activity suppression ratio n.s. n.s. F1,43 = 0.211, p = 0.6482 F1,38 = 1.274, p = 0.2662 Fig. 8f, l
Cued test 1 month after conditioning (CS) Activity suppression ratio n.s. n.s. F1,41 = 3.032, p = 0.0891 F1,38 = 1.046, p = 0.3129 Fig. 8f, l

n.s. no significance

Nominal significance: +/− p < 0.05, + +/− − p < 0.01, + + +/− − − p < 0.001