Phenotypes Associated with This Genotype

Genotype
MGI:6157969

• Allelic Composition: Tcf4^em1Bdph/?
• Genetic Background: involves: C57BL/6 * C57BL/6J

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

growth/size/body

decreased body weight ( J:254983 )

microcephaly ( J:254983 )

behavior/neurological

impaired spatial learning ( J:254983 )

• mice take a longer time to locate the hidden platform in the Morris water maze task and travel farther during the acquisition phase than controls

• however, during the reversal phase of the hidden platform test, mice perform similar to controls

decreased anxiety-related response ( J:254983 )

• mice spend more time in the center region of the novel open field during the last 20 min of the trial, indicating reduced anxiety

• in the elevated plus maze task, mice spend more time in the open arms and make more entries into the open arm than closed arm, indicating reduced anxiety

decreased startle reflex ( J:254983 )

• mice exhibit decreases in the startle amplitude across a range of sound levels at 7-11 weeks of age, but only mild deficits to the acoustic startle stimulus alone by 16 weeks of age, indicating a dampened response with age

increased locomotor activity ( J:254983 )

• mice exhibit increased activity and total distance traveled in the open field task

• however, mice exhibit normal motor coordination in the accelerating rotarod and normal sociability in the three-chamber task

nervous system

abnormal brain morphology ( J:254983 )

• reduction in brain volume

decreased brain weight ( J:254983 )

abnormal action potential ( J:254983 )

• CA1 pyramidal neurons produce fewer action potentials across a series of depolarizing current steps, indicating reduced firing rates

• action potentials in CA1 pyramidal neurons are initiated at a more depolarized membrane potential relative to controls

• CA1 pyramidal neurons have s slower rate of action potential rise and diminished action potential amplitude

• however, passive membrane properties of CA1 pyramidal neurons are unaffected

enhanced NMDA-mediated synaptic currents ( J:254983 )

• NMDA/AMPA current ratio is enhanced and because AMPA receptor-mediated synaptic transmission appears intact, this suggests that NMDAR-mediated currents are selectively enhanced

• mice exhibit an increase in the decay time of the NMDAR-mediated component of the EPSC

• sensitivity of NMDAR-mediated currents in CA1 pyramidal cells to the NR2B-selective antagonist ifenprodil is increased

enhanced long-term potentiation ( J:254983 )

• mice exhibit enhanced hippocampal long term potentiation (LTP) after 3 1 second bursts of 100 Hz stimulation and LTP is consistently enhanced over a range of stimulation frequencies

• however, no differences in long term depression (LTD) after 15 min of 1 Hz stimulation are seen, presynaptic function and AMPA receptor-mediated synaptic transmission appear normal in hippocampal area CA1, and short-term plasticity in terms of the paired-pulse ratio appears normal

increased prepulse inhibition ( J:254983 )

• percentage prepulse inhibition is enhanced in 7-11 week old mice but not 16-week old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Pitt-Hopkins syndrome		DOID:0060488	OMIM:610954	J:254983