Phenotypes associated with this allele

• Allele Symbol: Dlg3^tm1Grnt
• Allele Name: targeted mutation 1, Seth G N Grant
• Allele ID: MGI:3706312
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Dlg3^tm1Grnt/Y Dlg4^tm1Grnt/Dlg4^tm1Grnt	involves: 129P2/OlaHsd * MF1	MGI:3707224
cx2	Dlg3^tm1Grnt/Dlg3^+ Dlg4^tm1Grnt/Dlg4^tm1Grnt	involves: 129P2/OlaHsd * MF1	MGI:3707225
cx3	Dlg3^tm1Grnt/Dlg3^tm1Grnt Dlg4^tm1Grnt/Dlg4^tm1Grnt	involves: 129P2/OlaHsd * MF1	MGI:3707226
ot4	Dlg3^tm1Grnt/Y	involves: 129P2/OlaHsd * C57BL/6J	MGI:5824730
ot5	Dlg3^tm1Grnt/Y	involves: 129P2/OlaHsd * MF1	MGI:3707223

Genotype
MGI:3707224

cx1

• Allelic Composition: Dlg3^tm1Grnt/Y; Dlg4^tm1Grnt/Dlg4^tm1Grnt
• Genetic Background: involves: 129P2/OlaHsd * MF1

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

perinatal lethality, complete penetrance ( J:120078 )

♂ • no Dlg3^tm1Grnt/y, Dlg4-null male mice mice are produced by crosses of heterozygous Dlg3 and Dlg4 mice; double mutants die perinatally

Genotype
MGI:3707225

cx2

• Allelic Composition: Dlg3^tm1Grnt/Dlg3⁺; Dlg4^tm1Grnt/Dlg4^tm1Grnt
• Genetic Background: involves: 129P2/OlaHsd * MF1

mortality/aging

perinatal lethality, incomplete penetrance ( J:120078 )

♀ • crosses of heterozygous Dlg3 and Dlg4 mice produce a very low proportion of Dlg3^tm1Grnt/+, Dlg4-null female mice

Genotype
MGI:3707226

cx3

• Allelic Composition: Dlg3^tm1Grnt/Dlg3^tm1Grnt; Dlg4^tm1Grnt/Dlg4^tm1Grnt
• Genetic Background: involves: 129P2/OlaHsd * MF1

mortality/aging

perinatal lethality, complete penetrance ( J:120078 )

♀ • crosses of heterozygous Dlg3 and Dlg4 mice produce no double homozygotes; double mutants die perinatally with none surviving past day 3 postnatal

Genotype
MGI:5824730

ot4

• Allelic Composition: Dlg3^tm1Grnt/Y
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

nervous system

abnormal brain morphology ( J:238576 )

♂ • brain mass is reduced

abnormal neocortex size ( J:238576 )

♂ • total neocortical area is reduced

abnormal somatosensory cortex morphology ( J:238576 )

♂ • reduction in the total numbers of thalamocortical axons innervating the somatosensory cortex

♂ • however, segregation of barrels is unaffected

abnormal barrel cortex morphology ( J:238576 )

♂ • area of posteromedial barrel subfield is reduced

♂ • combined area of all thalamocortical axon patches in the barrel cortex is reduced indicating a reduction in thalamocortical innervation of barrel cortex

abnormal innervation ( J:238576 )

♂ • P8-10 mice show a reduction in connectivity of individual thalamocortical axons onto L4 neurons despite normal NMDA receptor function after the critical period

♂ • reduction in neurofilament medium polypeptide-positive axons in barrel cortex in P6-7 mice

abnormal axon morphology ( J:238576 )

♂ • decrease in the number of thalamocortical axons

abnormal synapse morphology ( J:238576 )

♂ • thalamocortical synapses transiently show altered NMDA receptor function

♂ • however, after the critical period thalamocortical synapses function normally

decreased excitatory postsynaptic current amplitude ( J:238576 )

♂ • reduction in peak excitatory postsynaptic current (EPSC) amplitude

♂ • however, no differences are seen in minimal stimulation EPSC amplitude

prolonged excitatory postsynaptic current decay time ( J:238576 )

♂ • NMDA excitatory postsynaptic currents (EPSCs) show faster decay kinetics during the critical period for thalamocortical plasticity

♂ • treatment with ifenprodil, a GluN2B-specific antagonist, has no effect on NMDA EPSCs

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
non-syndromic X-linked intellectual disability		DOID:0050776	OMIM:300716 OMIM:PS309530	J:238576

Genotype
MGI:3707223

ot5

• Allelic Composition: Dlg3^tm1Grnt/Y
• Genetic Background: involves: 129P2/OlaHsd * MF1

behavior/neurological

abnormal spatial learning ( J:120078 )

♂ • in Morris water maze test, with a visible, elevated platform, mutants' speed in reaching platform improves on day 2 and 3 of training whereas wild-type mice do not improve

♂ • in hidden platform paradigm, wild-type mice show improvement in performance over 5 days of training, while mutants do not

♂ • in a reversal platform protocol, mutants show a gradual improvement after 6 days, while wild-type learn the new platform position in the first block of training; retention of information on platform position is retained for 2 weeks, but by 8 weeks after training, mutants' performance is back to chance levels

♂ • in visible version of task, mutants use the approaching strategy, while wild-type use a less efficient self-orienting strategy; in the hidden (ie. hippocampus-dependent) version, mutants use a less efficient circling strategy, whereas wild-type use the approaching strategy, and with training switch to the direct finding strategy

abnormal locomotor activation ( J:120078 )

♂ • in assessment of motor abilities, mutants show an slightly altered locomotor phenotype measured by some differences in the rotarod, open field and elevated plus maze tests

nervous system

abnormal long-term potentiation ( J:120078 )

♂ • induction of LTP with conventional high-frequency protocol is similar in wild-type and mutant hippocampal slices; long-low-frequency train of synaptic stimulation produces a 2-fold increase in synaptic strength in mutant slices compared to only modest LTP in wild-type slices

♂ • pairing of single pulses of presynaptic fiber stimulation with single postsynaptic action potentials induces robust LTP in mutant cells but does not in wild-type cells