Phenotypes Associated with This Genotype

Genotype
MGI:6479882

• Allelic Composition: Tcf4^tm1Zhu/Tcf4⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/SvImJ * C57BL/6J

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

behavior/neurological

impaired contextual conditioning behavior ( J:239016 )

• mice show reduced freezing in the contextual fear conditioning tests

• mice treated subchronically with suberoylanilide hydroxamic acid show rescue of memory-associated freezing in the contextual and cued tests

impaired cued conditioning behavior ( J:239016 )

• mice show reduced freezing in the cued fear conditioning test

• mice treated subchronically with suberoylanilide hydroxamic acid show rescue of memory-associated freezing in the contextual and cued tests

impaired spatial learning ( J:239016 )

• in the Morris water maze, mice fail to show selectivity for the target quadrant, spending less time there than wild-type mice and crossing the platform zone fewer times

abnormal long-term spatial reference memory ( J:239016 )

• mice have a deficit in the 24 hour object location memory indicating impaired spatial memory

increased grooming behavior ( J:239016 )

• mice groom themselves more than wild-type mice

increased startle reflex ( J:239016 )

• mice exhibit enhanced startle reflex to unexpected 120 dB sound bursts

impaired balance ( J:239016 )

• mice exhibit asymmetry in their motor control and an imbalance that favors their left size

• however, mice show no differences on the rotating rod or in walking across a horizontal ladder

decreased grip strength ( J:239016 )

• mice show weaker hindlimb, but not forelimb, grip strength

abnormal gait ( J:239016 )

• mice favor their front left paw while ambulating across a catwalk

• dynamic weight bearing analysis indicates that mice place more weight on their front left paw than their right paw

increased locomotor activity ( J:239016 )

• however, mice do not show an increase in anxiety in the open field or elevated plus maze

• mice show increased activity in the open field and in the elevated plus maze, where mice show an increase in overall arm entrances

social withdrawal ( J:239016 )

• mice prefer social isolation over interaction with a novel mouse in the three-chamber social test

decreased vocalization ( J:239016 )

• pups have reduced ultrasonic vocalization when removed from the nest, which remains low until the phenotype converges with normal behavior or wild-type controls around P7

• P3 pups have weaker calls

• P3 pups have less frequent ultrasonic distress calls and at lower volumes

nervous system

enhanced long-term potentiation ( J:239016 )

• mice exhibit enhanced Schaffer collateral long-term potentiation when activated with theta burst stimulation

• hippocampal CA1 area treated with the HDAC inhibitor Trichostatin A before theta burst stimulation normalizes the LTP

decreased prepulse inhibition ( J:239016 )

• mice have deficits in prepulse inhibition

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Pitt-Hopkins syndrome		DOID:0060488	OMIM:610954	J:239016