G2C::Genetics

Mutation

Generation of Dlg4 mutant mice described in Arbuckle et al (2010)

Overview

Mutant mice showed little overall behavioural difference from wildtypes, with two of 16 behaviour variables significantly impacted in these mutants. In the elevated plus maze task, one behavioural variable, EPM total distance, was significantly increased in mutants. In the rotarod task, one behavioural variable, RR learning, was significantly increased in mutants. Open field/novel object exploration, fear learning, contextual memory and cued memory tasks were unaffected. Definitions of variables may be found below.

The G2CMine data warehouse provides cohort summaries and individual mouse observations from the PSD-95-SH3 point line phenotyping.

 

Variables shown are: EPM total distance, Total distance (cm) travelled in any arm or central zone of the EPM. EPM max speed, Maximum speed (cm/s) travelled in any arm or central zone of the EPM. EPM % time in open, Percentage of time in the open or closed arms of the EPM spent in open arms. EPM time in centre, Total time (s) spent in the central zone of the EPM. EPM max speed, open vs closed, Difference between the maximum speed (cm/s) observed in the open arms and the closed arms of the EPM. OF, NOE total distance, Total distance travelled (log₁₀ cm) during initial exposure to the open field and in presence of the novel object. NOE vs OF distance travelled, Difference in distance travelled (cm) in presence of the novel object and during initial exposure to open field. RR naive fall time, Fall time on accelerating rotarod (log₁₀ s), naive performance in session 1. RR learning, Learning on rotarod, measured as increase in fall time per trial (s/trial) in session 1. RR memory, Memory on rotarod, measured as excess fall time at middle of session 2 relative to middle of session 1. Fear learning, trial effect, Fear learning, measured as extra % time freezing before third trial compared to % time freezing before first trial. Fear learning, tone effect, Fear learning, measured as increase in % time freezing due to third tone compared to increase in % time freezing due to first tone. Contextual memory, mean, Contextual memory, measured as difference in % time freezing during first 120 s re-exposure to the box compared to first 120 s in the box on previous day. Contextual memory, change, Contextual memory, measured as increase in % time spent freezing from first time bin of 30 s to fourth bin of 30 s during 120 s re-exposure to the box. Cued memory, mean, Cued memory, measured as increase in % time spent freezing during 120 s of tone re-exposure compared to increase in % time spent freezing during initial tone on previous day. Cued memory, change, Cued memory, measured as increase in % time spent freezing from first time bin of 30 s to fourth bin of 30 s during 120 s re-exposure to the tone.

 

Variable	Units	Wildtype M (n=10)	Wildtype F (n=11)	Mutant M (n=11)	Mutant F (n=10)	P(sex×mutation)	P(mutation)
EPM total distance	cm	1267 (41)	1237 (83)	1436 (68)	1378 (100)	0.85	0.049 *
EPM max speed	cm/s	24.2 (1.1)	25.1 (1.1)	25.8 (1)	26.5 (1.3)	0.94	0.19
EPM % time in open	%	15.8 (2.6)	12.9 (2.9)	16.4 (3)	12.7 (3)	0.89	0.95
EPM time in centre	s	58.6 (3.2)	57.5 (6.8)	63.6 (4.2)	59.6 (6.2)	0.78	0.51
EPM max speed, open vs closed	cm/s	-6.2 (1.3)	-7.4 (1.3)	-5.3 (1.4)	-9 (2.3)	0.46	0.83
OF, NOE total distance	log10 cm	3.64 (0.02)	3.71 (0.02)	3.69 (0.02)	3.75 (0.04)	0.87	0.13
NOE vs OF distance travelled	cm	-1010 (210)	-1040 (180)	-1130 (210)	-800 (170)	0.36	0.76
RR naive fall time	log10 s	1.47 (0.1)	1.83 (0.07)	1.42 (0.08)	1.59 (0.08)	0.26	0.084
RR learning	s/trial	6.4 (1.9)	5.2 (1.1)	8.2 (1.2)	12.4 (2.2)	0.099	0.0089 **
RR memory	s	24.2 (5.1)	22.1 (6.3)	25.3 (4.8)	45.1 (11.2)	0.14	0.1
Fear learning, trial effect	% freezing	42.1 (3.7)	35.3 (5.7)	38.9 (6.7)	48.7 (8.1)	0.19	0.43
Fear learning, tone effect	% freezing	-3.1 (5.8)	-1.8 (5.3)	-0.9 (3)	2.9 (5.8)	0.8	0.5
Contextual memory, mean	% freezing	41.2 (5.9)	21.4 (8.1)	22.5 (3.8)	29.6 (7.5)	0.047 *	0.43
Contextual memory, change	% freezing	7.2 (9.6)	9.1 (7.2)	2.2 (6.6)	5.6 (8.7)	0.92	0.6
Cued memory, mean	% freezing	7.9 (9.7)	10 (5.4)	18.2 (5.3)	21.9 (9.1)	0.91	0.15
Cued memory, change	% freezing	10.5 (7)	-11.3 (6.7)	-8.8 (5.2)	-4 (5.3)	0.035 *	0.33

Overview

Mutant slices showed little overall electrophysiological difference from wildtype slices, with no electrophysiological variables significantly affected by this mutation. Note that in the theta burst analysis, the tenth burst is analysed as representative of individual burst amplitude.

The G2CMine data warehouse provides slice group summaries and individual mouse observations from the PSD-95-SH3 point line phenotyping.