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

From: A network model of genomic hormone interactions underlying dementia and its translational validation through serendipitous off-target effect

Name Mutation category Observed effects on the nervous system Ratio of KO studies with CNS phenotypes to studies without CNS phenotypes
Estrogen signaling  
Esr1tm1Ksk Targeted (knock-out) abnormal pituitary gland physiology 4:8 (50%)
abnormal hypothalamus morphology
abnormal innervation
Ncor2tm1Kjep Targeted (knock-out) abnormal cerebral cortex morphology 1:0 (100%)
abnormal neuron differentiation
Hdac2tm1.2Rdp Targeted (knock-out) abnormal hippocampus CA1 region morphology 1:3 (34%)
abnormal dentate gyrus morphology
abnormal hippocampus pyramidal cell morphology
enhanced long term potentiation
Ccnd1tm1Wbg Targeted (knock-out) absent Purkinje cell layer 1:3 (34%)
abnormal cerebellar granule layer
small cerebellum
Crebbptm1Sis Targeted (knock-out) abnormal forebrain morphology 3:4 (75%)
Insulin signaling  
Juntm1Wag Targeted (knock-out) abnormal forebrain morphology 1:2 (50%)
Hras1tm1Grnt Targeted (knock-out) reduced long term potentiation 1:3 (34%)
Csnk2a1 Targeted (knock-out) abnormal telencephalon development 1:2 (50%)
Mapk3tm1Gpg Targeted (knock-out) reduced long term potentiation 2:2 (100%)
Leptin signaling pathway
Leprtm1.2Chua Targeted (knock-out) abnormal inhibitory postsynaptic currents 1:4 (25%)
Stat3tm1Aki Targeted (knock-out) abnormal motor neuron morphology 1:6 (17%)
abnormal neuron physiology
Hif1atm1.1Stom 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
Rxrbtm1Rev Targeted (knock-out) abnormal excitatory postsynaptic potential 2:3 (67%)
reduced long term potentiation
absent long term depression
Corticotropin-releasing pathway
Gnaqtm1Soff Targeted (knock-out) abnormal glutamate-mediated receptor currents 1:2 (50%)
absent long term depression
Braftm1.1Sva Targeted (knock-out) increased neuron apoptosis 3:3 (100%)
abnormal innervation
thin cerebral cortex
Nos1tm1Plh 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
Gnai1tm1Drs Targeted (knock-out) abnormal long term potentiation 1:1 (100%)
Plcb1tm1Hssh Targeted (knock-out) loss of hippocampal neurons 1:1 (100%)
Creb1tm1Gsc Targeted (knock-out) abnormal CNS synaptic transmission 1:2 (50%)
   reduced long term potentiation