Mouse Genome Informatics
hm1
    Syngap1tm1Rlh/Syngap1tm1Rlh
involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging


Mouse Genome Informatics
hm2
    Syngap1tm1Rlh/Syngap1tm1Rlh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• pups die between P5 and P7

growth/size/body
• between P4 and P6, pups stay small in size

behavior/neurological
• by P3, pups do not feed from the mother
• by P3, homozygous mutants show less movement

nervous system
• homozygotes had significantly fewer morphological silent synapses (synapses that contain NMDA receptors but not AMPA receptors) and had a greater number of AMPA receptor clusters in cortical neuronal cultures


Mouse Genome Informatics
ht3
    Syngap1tm1Rlh/Syngap1+
involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants exhibit random vectors through the open field unlike wild-type mice that primarily run around the outside chamber and spend most of the time in the corners, indicating abnormal anxiety levels
• mutants are more likely to venture into the center of the field during the first few minutes of the test session, indicating decreased thigmotaxis
• in the elevated plus maze, mutants spend less time in the closed arm and more time in the open arm compared to wild-type mice, indicating decreased anxiety levels
• mutants exhibit reduced freezing in response to a conditioning tone previously associated with a mild footshock, however the freezing response is intact as behavioral responses to a fear-associated context are normal
• activity during conditioning tone presentation is normal, however activity is elevated during tone presentation in the retrieval test
• although mutants are able to learn forced alteration rule in the automated eight-arm radial maze, mutants show a time-dependent decrease in nonmatching performance, indicating spatial working memory deficits
• mutants respond more strongly to the 120 dB stimulus then wild-type mice
• mutants show enhanced startle responses at the highest amplitudes (loudest pulses)
• mutants exhibit elevated horizontal activity compared to wild-type littermates and this behavior is nonhabituating over repeated trials
• juvenile, newly weaned mutants also exhibit increased horizontal activity
• antipsychotic drug clozapine ameliorates the persistent hyperactivity
• the NMDAR antagonist, MK-801, has a reduced effect on hyperactivity in mutants compared to wild-type mice
• mutants show an increase in stereotypies in the open field test compared to wild-type littermates, most pronounced at the beginning of a 2 hour test session
• mutants show increased stereotypic behavior in 30 minute open field trials over 5 consecutive days, indicating behavior is nonhabituating
• mutants are unable to distinguish between familiar and novel conspecifics compared to wild-type mice which spend more time with the novel conspecifics
• in a test for social isolation, mutants spend more time in the center compartment (a space that is separated from the other mice) than in ends of chamber where novel conspecifics were placed, indicating a preference for social isolation

nervous system

Mouse Models of Human Disease
OMIM IDRef(s)
Schizophrenia; SCZD 181500 J:194146


Mouse Genome Informatics
ht4
    Syngap1tm1Rlh/Syngap1+
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• at P14, mice exhibit normal medial perforant path release probability and intrinsic spiking of dentate gyrus neurons (J:193208)
• at P14, dentate gyrus neuron dendritic trees exhibit a decrease in the spatial volume compared with in wild-type mice
• larger spines by P14 and persisting into adulthood
• more mushroom-type spines and fewer stubby spines beginning in the second postnatal week
• spines are less motile at P14
• some spines exhibit a spontaneous increase in head volume
• however, spine density is normal
• photosimulation-evoked signals originating in the dentate gyrus are amplified as they spread through the hippocampus unlike in wild-type mice
• synaptic transmission in the Schaeffer Collateral pathway in the CA1 is strong during early development compared with wild-type mice
• however, synaptic transmission in the Schaeffer Collateral pathway in the CA1 in adult mice is normal
• by P14, field excitatory postsynaptic potential is increased compared to in control mice
• however, synaptic function at P9, P21 and later is normal
• at P14, mice exhibit an increase in the ratio of AMPA/NMDA currents in dentate gyrus granule neurons compared with wild-type mice
• however, NMDAR-evoked synaptic transmission is normal
• increased sensitivity at P14
• increased amplitude and frequency at P14
• however, both are normal at P21
• increased frequency and amplitude in the dentate gyrus neurons

behavior/neurological
N
• mice exhibit normal contextual fear memory (J:193208)
• mice are unable to discriminate between two contexts during contextual fear training unlike wild-type mice
• in an open field at P14


Mouse Genome Informatics
ht5
    Syngap1tm1Rlh/Syngap1+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• long term potentiation induced by TBS was significantly decreased in the CA1 region of hippocampal slices, however there was no difference in the magnitude of long term depression