Phenotypes Associated with This Genotype

Genotype
MGI:7261388

• Allelic Composition: Tshz3^tm2.1Lafa/Tshz3^tm2.1Lafa; Tg(Camk2a-cre)2Gsc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

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

behavior/neurological

abnormal behavior ( J:294534 )

• mice show reduced field of interest with smaller number of zone crossings in the open field

increased thigmotaxis ( J:294534 )

• mice exhibit increased anxiety-like behavior, avoiding the central area more in the open field and in the open arms of the elevated plus maze

• however, mice learn normally in the Morris water maze, mice show normal hind paw coordination, and do not show visual, auditory, or olfactory deficits

increased stereotypic behavior ( J:294534 )

• mice bury more marbles and dip more repeatedly in the hole board

abnormal social investigation ( J:294534 )

• mice exhibit lower sociability in the two-chamber test

abnormal response to social novelty ( J:294534 )

• mice show lower interest in social novelty in the two-chamber test

nervous system

abnormal action potential ( J:294534 )

• the inter-action potential intervals in response to a threshold current step (+150 pA, just above the rheobase) are longer in cortical projection neurons, suggesting increased accommodation and, possibly, decreased excitability

• however, the inter-action potential interval in response to a strong depolarizing current (+300 pA) is similar to controls and while cortical projection neurons show a lower number of action potentials in response to depolarizing current pulses, this is not significantly different from controls

• no major changes in membrane properties of cortical projection neurons and in the proportion of pyramidal tract versus intratelencephalic neurons are seen

abnormal synaptic transmission ( J:294534 )

• the NMDA/AMPA ratio is increased in spiny projection neurons

abnormal excitatory postsynaptic currents ( J:294534 )

• the paired-pulse ratio of AMPA receptor-mediated excitatory postsnynaptic currents (EPSCs) in layer 5 (L5) cortical projection neurons is higher, suggesting a decreased probability of action potential-dependent glutamate release from L2/3 cortical neurons

• however, the paired-pulse ratio of GABAergic inhibitory postsynaptic currents is similar to controls and the distribution of miniature EPSC interevent interval and amplitude, as well as the average frequency and amplitude, and the NMDA/AMPA ratio are similar to controls

• the paired-pulse ratio of corticostriatal glutamatergic EPSCs is higher in spiny projection neurons, suggesting a decreased probability of action potential-dependent glutamate release from L5 cortical projection neurons

• however, striatal spiny projection neurons present similar resting membrane potential and current-voltage relationship as controls and miniature EPSC parameters are not changed in spiny projection neurons

absent long-term depression ( J:294534 )

• long-term depression (LTD) is absent and is even reversed as a transient potentiation

• however, long-term potentiation is normal

• the blockade of NMDA receptors by AP-5 partially recovers LTD and abolishes the transient potentiation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:294534