Table 4 Knockout mouse phenotypes observed for several proteins in the core DHN model

Esr1^tm1Ksk

Targeted (knock-out)

abnormal pituitary gland physiology

4:8 (50%)

abnormal hypothalamus morphology

abnormal innervation

Ncor2^tm1Kjep

Targeted (knock-out)

abnormal cerebral cortex morphology

1:0 (100%)

abnormal neuron differentiation

Hdac2^tm1.2Rdp

Targeted (knock-out)

abnormal hippocampus CA1 region morphology

1:3 (34%)

abnormal dentate gyrus morphology

abnormal hippocampus pyramidal cell morphology

enhanced long term potentiation

Ccnd1^tm1Wbg

Targeted (knock-out)

absent Purkinje cell layer

1:3 (34%)

abnormal cerebellar granule layer

small cerebellum

Crebbp^tm1Sis

Targeted (knock-out)

abnormal forebrain morphology

3:4 (75%)

Insulin signaling

Jun^tm1Wag

Targeted (knock-out)

abnormal forebrain morphology

1:2 (50%)

Hras1^tm1Grnt

Targeted (knock-out)

reduced long term potentiation

1:3 (34%)

Csnk2a1

Targeted (knock-out)

abnormal telencephalon development

1:2 (50%)

Mapk3^tm1Gpg

Targeted (knock-out)

reduced long term potentiation

2:2 (100%)

Leptin signaling pathway

Lepr^tm1.2Chua

Targeted (knock-out)

abnormal inhibitory postsynaptic currents

1:4 (25%)

Stat3^tm1Aki

Targeted (knock-out)

abnormal motor neuron morphology

1:6 (17%)

abnormal neuron physiology

Hif1a^tm1.1Stom

Targeted (knock-out)

abnormal cerebrum morphology

4:7 (57%)

abnormal cerebral cortex morphology

loss of cortex neurons

abnormal occipital lobe morphology

abnormal temporal lobe morphology

loss of hippocampal neurons

Thyroid signaling pathway

Rxrb^tm1Rev

Targeted (knock-out)

abnormal excitatory postsynaptic potential

2:3 (67%)

reduced long term potentiation

absent long term depression

Corticotropin-releasing pathway

Gnaq^tm1Soff

Targeted (knock-out)

abnormal glutamate-mediated receptor currents

1:2 (50%)

absent long term depression

Braf^tm1.1Sva

Targeted (knock-out)

increased neuron apoptosis

3:3 (100%)

abnormal innervation

thin cerebral cortex

Nos1^tm1Plh

Targeted (knock-out)

abnormal brain wave pattern

3:4 (75%)

abnormal long term potentiation

reduced long term potentiation

absent long term depression

decreased synaptic glutamate release

abnormal peripheral nervous system regeneration

Melatonin signaling pathway

Gnai1^tm1Drs

Targeted (knock-out)

abnormal long term potentiation

1:1 (100%)

Plcb1^tm1Hssh

Targeted (knock-out)

loss of hippocampal neurons

1:1 (100%)

Creb1^tm1Gsc

Targeted (knock-out)

abnormal CNS synaptic transmission

1:2 (50%)

reduced long term potentiation