Phenotypes associated with this allele

• Allele Symbol: Emx1^tm1(cre)Krj
• Allele Name: targeted mutation 1, Kevin R Jones
• Allele ID: MGI:2684610
• Summary: 76 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Emx1^tm1(cre)Krj/Emx1^tm1(cre)Krj	involves: 129S2/SvPas * C57BL/6	MGI:2684615
cn2	Emx1^tm1(cre)Krj/Emx1^+ Ptpn11^tm6Bgn/Ptpn11^+	B6.129S-Ptpn11^tm6Bgn Emx1^tm1(cre)Krj	MGI:6095197
cn3	Slc17a6^tm1.1Jder/Slc17a6^tm1.1Jder Emx1^tm1(cre)Krj/Emx1^+	B6.Cg-Emx1^tm1(cre)Krj Slc17a6^tm1.1Jder	MGI:5469863
cn4	Glul^tm1.1Ncd/Glul^tm1.1Ncd Emx1^tm1(cre)Krj/Emx1^+	B6.Cg-Glul^tm1.1Ncd Emx1^tm1(cre)Krj	MGI:6285755
cn5	Magoh^tm1c(KOMP)Dlsi/Magoh^+ Emx1^tm1(cre)Krj/Emx1^+	B6.Cg-Magoh^tm1c(KOMP)Dlsi Emx1^tm1(cre)Krj	MGI:5695285
cn6	Emx1^tm1(cre)Krj/? Rai1^tm2.1Luo/Rai1^tm2.1Luo	either: (involves: 129S1/Sv * 129S2/SvPas * C57BL/6) or (involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6)	MGI:5817664
cn7	Pdcd10^tm1Wami/Pdcd10^tm1Wami Emx1^tm1(cre)Krj/Emx1^+	involves: 129 * 129S2/SvPas * C57BL/6	MGI:5002699
cn8	Celf4^tm1.1Frk/Celf4^tm1.1Frk Emx1^tm1(cre)Krj/?	involves: 129 * C57BL/6J	MGI:6194753
cn9	Celsr3^tm1Agof/Celsr3^tm2Agof Emx1^tm1(cre)Krj/Emx1^+	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3795740
cn10	Nrg1^tm1Fej/Nrg1^tm1Fej Emx1^tm1(cre)Krj/?	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3835560
cn11	Tor1a^tm2Wtd/Tor1a^tm3.1Wtd Tor1b^tm1.2Wtd/Tor1b^tm1.2Wtd Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:6710961
cn12	Tor1a^tm1Wtd/Tor1a^tm3.1Wtd Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:5605975
cn13	Tor1a^tm1Wtd/Tor1a^tm3.1Wtd Tor1b^tm1.2Wtd/Tor1b^tm1.1Wtd Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:6710955
cn14	Tor1a^tm2Wtd/Tor1a^tm3.1Wtd Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:6710956
cn15	Tor1a^tm2Wtd/Tor1a^tm3.1Wtd Tor1b^tm1.2Wtd/Tor1b^+ Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:6710960
cn16	Celsr1^tm1Fati/Celsr1^tm1Fati Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:4430220
cn17	Pals1^tm1Caw/Pals1^tm1Caw Tsc2^tm1.1Mjg/Tsc2^tm1.1Mjg Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:4459298
cn18	Slc12a2^tm1.1Jheb/Slc12a2^tm1.1Jheb Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:5538342
cn19	Pax6^tm2Pgr/Pax6^tm2Pgr Smarcc2^tm1.1Stoy/Smarcc2^tm1.1Stoy Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:5504444
cn20	Pax6^tm2Pgr/Pax6^tm2Pgr Smarcc2^tm1.1Stoy/Smarcc2^+ Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:5504443
cn21	Bptf^tm1.1Cwu/Bptf^tm1.1Cwu Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:7518724
cn22	Pnkp^tm1.1Pmc/Pnkp^tm1.1Pmc Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:5795755
cn23	Smarcc2^tm1.1Stoy/Smarcc2^tm1.1Stoy Emx1^tm1(cre)Krj/Emx1^+	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:5504445
cn24	Emx1^tm1(cre)Krj/Emx1^+ Tg(CMV-GFP,-Smarcc2,-lacZ)#Stoy/0	involves: 129S2/SvPas	MGI:5504448
cn25	Emx1^tm1(cre)Krj/Emx1^+ Wnt3a^tm2Eag/Wnt3a^+	involves: 129S2/SvPas	MGI:3616432
cn26	Dact1^tm1.1Bnrc/Dact1^tm1.2Bnrc Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas	MGI:4442996
cn27	Pals1^tm1Caw/Pals1^tm1Caw Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas	MGI:4459295
cn28	Pals1^tm1Caw/Pals1^+ Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas	MGI:4459297
cn29	Orc3^tm1.1Zhua/Orc3^tm1.1Zhua Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas	MGI:4947981
cn30	Sp2^tm1.1Htg/Sp2^tm1.1Htg Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas	MGI:5471312
cn31	Pomt2^tm1.1Hhu/Pomt2^tm1.1Hhu Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J	MGI:5302860
cn32	Rem2^tm1c(EUCOMM)Hmgu/Rem2^tm1c(EUCOMM)Hmgu Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6N	MGI:6192624
cn33	Knl1^tm1c(EUCOMM)Hmgu/Knl1^tm1c(EUCOMM)Hmgu Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6N	MGI:6358251
cn34	Zfp335^tm1.1Caw/Zfp335^tm1.1Caw Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:5470140
cn35	Zfp335^tm1.1Caw/Zfp335^+ Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:5470141
cn36	Bhlhe22^tm2.1Meg/Bhlhe22^tm2.1Meg Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:5315767
cn37	Islr2^tm1.1Ddg/Islr2^tm2.1Ddg Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * SJL	MGI:5569795
cn38	Atxn1^tm2Hzo/Atxn1^tm2Hzo Atxn1l^tm2Hzo/Atxn1l^tm2Hzo Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S7/SvEvBrd	MGI:6275610
cn39	Epha4^tm1.1Bzh/Epha4^tm1.2Bzh Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129S7/SvEvBrd	MGI:5614429
cn40	Itgb1^tm1Mll/Itgb1^tm1Mll Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129X1/SvJ	MGI:4947982
cn41	Adcy3^tm2.1Drs/Adcy3^tm2.1Drs Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129X1/SvJ	MGI:7260161
cn42	Rnu11^tm1.1Rank/Rnu11^tm1.1Rank Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * 129X1/SvJ	MGI:6393904
cn43	Emx1^tm1(cre)Krj/Emx1^+ Numb^tm1Ynj/Numb^tm1Ynj	involves: 129S2/SvPas * 129X1/SvJ * CD-1	MGI:3582334
cn44	Emx1^tm1(cre)Krj/Emx1^+ Numb^tm1Ynj/Numb^tm1Ynj Numbl^tm1Wmz/Numbl^tm1Wmz	involves: 129S2/SvPas * 129X1/SvJ * CD-1	MGI:3582335
cn45	Pik3r4^mbe/Pik3r4^tm1.1Mpnd Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C3H/HeH * C57BL/6	MGI:6331079
cn46	Emx1^tm1(cre)Krj/Emx1^+ Mycbp2^tm1Adia/Mycbp2^tm1Adia	involves: 129S2/SvPas * C57BL/6	MGI:3760657
cn47	Pik3r4^tm1.1Mpnd/Pik3r4^tm1.1Mpnd Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6	MGI:6331087
cn48	Emx1^tm1(cre)Krj/? Kcnq2^tm1.1Avtz/Kcnq2^tm1.1Avtz	involves: 129S2/SvPas * C57BL/6	MGI:5607737
cn49	Emx1^tm1(cre)Krj/? Kcnq3^tm1.1Avtz/Kcnq3^tm1.1Avtz	involves: 129S2/SvPas * C57BL/6	MGI:5607738
cn50	Cic^tm1c(KOMP)Wtsi/Cic^tm1c(KOMP)Wtsi Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6 * C57BL/6N	MGI:6275604
cn51	Bdnf^tm1Krj/Bdnf^+ Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:3584257
cn52	Ppp4r3a^em1Qili/Ppp4r3a^em1Qili Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:7312047
cn53	Emx1^tm1(cre)Krj/Emx1^+ Magoh^tm1c(KOMP)Dlsi/Magoh^+	involves: 129S2/SvPas * C57BL/6J	MGI:7335202
cn54	Emx1^tm1(cre)Krj/Emx1^+ Rbm8a^tm1Dlsi/Rbm8a^+	involves: 129S2/SvPas * C57BL/6J	MGI:7335203
cn55	Emx1^tm1(cre)Krj/Emx1^+ Topbp1^tm1Pmc/Topbp1^tm1Pmc	involves: 129S2/SvPas * C57BL/6J	MGI:5316226
cn56	Atr^tm2Bal/Atr^tm2Bal Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:5316224
cn57	Bdnf^tm1Krj/Bdnf^tm1Lfr Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:3584256
cn58	Eif4a3^tm1.1Dlsi/Eif4a3^+ Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:6382122
cn59	Nr2f1^tm2.1Mist/Nr2f1^tm2.1Mist Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J	MGI:5523193
cn60	Brpf1^tm1c(EUCOMM)Wtsi/Brpf1^tm1c(EUCOMM)Wtsi Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J * C57BL/6N	MGI:5896655
cn61	Afdn^tm1c(EUCOMM)Hmgu/Afdn^tm1c(EUCOMM)Hmgu Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J * C57BL/6N	MGI:5607285
cn62	Cmtr1^tm1b(EUCOMM)Hmgu/Cmtr1^tm1b(EUCOMM)Hmgu Emx1^tm1(cre)Krj/Emx1^+ Tg(Thy1-YFP)HJrs/0	involves: 129S2/SvPas * C57BL/6J * C57BL/6N * CBA	MGI:6502664
cn63	Kat6a^tm1c(EUCOMM)Wtsi/Kat6a^tm1c(EUCOMM)Wtsi Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6J * C57BL/6N * CD-1	MGI:5896662
cn64	Emx1^tm1(cre)Krj/Emx1^+ Rcor2^tm1c(EUCOMM)Wtsi/Rcor2^tm1c(EUCOMM)Wtsi	involves: 129S2/SvPas * C57BL/6N	MGI:5897782
cn65	Chn1^tm1Ito/Chn1^tm1.1Ito Emx1^tm1(cre)Krj/Emx1^+	involves: 129S2/SvPas * C57BL/6NSlc	MGI:5614424
cn66	Emx1^tm1(cre)Krj/Emx1^+ Lhx2^tm1.1Ddmo/Lhx2^tm1.2Ddmo	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4399056
cn67	Emx1^tm1(cre)Krj/Emx1^+ Lhx2^tm1.1Ddmo/Lhx2^tm1.1Ddmo	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4399057
cn68	Emx1^tm1(cre)Krj/Emx1^+ Esco2^tm1.1Ge/Esco2^tm1.1Ge	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:5308068
cn69	Cdh2^tm1Glr/Cdh2^tm1Glr Emx1^tm1(cre)Krj/Emx1^+	involves: 129S6/SvEvTac * C57BL/6	MGI:5607288
cn70	Emx1^tm1(cre)Krj/Emx1^+ Gsx2^tm2.1Kc/Gsx2^tm2.1Kc Tg(CAG-cat,-EGFP)1Rbns/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL	MGI:4412088
cn71	Emx1^tm1(cre)Krj/Emx1^+ Gsx2^tm2.1Kc/Gsx2^tm2.1Kc	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:4412086
cn72	Tsc2^tm1.1Kcess/Tsc2^tm1.1Kcess Emx1^tm1(cre)Krj/Emx1^+	involves: 129S/Sv * C57BL/6J	MGI:5496787
cn73	Gm30731^tm1.1Dalm/Gm30731^tm1.1Dalm Emx1^tm1(cre)Krj/Emx1^+	involves: 129S/SvEv * 129S2/SvPas * C57BL/6	MGI:6385155
cn74	Bhlhe22^tm2.1Meg/Bhlhe22^tm2.1Meg Emx1^tm1(cre)Krj/Emx1^+	involves: 129/Sv * 129S2/SvPas	MGI:4440904
cn75	Bicd2^tm1Hgrd/Bicd2^tm1Hgrd Emx1^tm1(cre)Krj/Emx1^+	involves: C57BL/6	MGI:5810138
cn76	Emx1^tm1(cre)Krj/Emx1^+ Rbm8a^tm1Dlsi/Rbm8a^+	involves: C57BL/6J	MGI:5803996

Genotype
MGI:2684615

hm1

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1^tm1(cre)Krj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

normal phenotype

no abnormal phenotype detected ( J:78098 )

• homozygous mice do not show any of the abnormal phenotypes shown for Emx1^tm1Jlr homozygotes

Genotype
MGI:6095197

cn2

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Ptpn11^tm6Bgn/Ptpn11⁺
• Genetic Background: B6.129S-Ptpn11^tm6Bgn Emx1^tm1(cre)Krj

behavior/neurological

impaired cued conditioning behavior ( J:242312 )

• during auditory cued retrieval, mice show a reduced ability to discriminate conditional stimuli of 10-kHZ, 10 seconds with 20 seconds inter stimulus intervals (CS+) and conditional stimuli of 2.5-kHz, 10 seconds with 20 seconds inter stimulus intervals (CS-), with response to CS+ slightly reduced and to CS- somewhat increased

• however, mice exhibit normal levels of contextual fear memory

decreased exploration in new environment ( J:242312 )

• mice exhibit reduced exploratory behavior in the open field task, with a shorter run distance than controls

abnormal spatial learning ( J:242312 )

• in the Morris water maze, mice show a reduced path length during training and lower average speed resulting in similar escape latencies as controls, and reduced total distance traveled during probe trial 1, indicating reduced memory specificity

nervous system

abnormal hippocampus neuron morphology ( J:242312 )

• surface expression and trafficking of synaptic glutamate receptors is altered in hippocampal neurons, indicating possible hippocampal neuronal plasticity defects

• however, axonal outgrowth and dendritic arborization in cultured hippocampal neurons is similar to controls and synaptogenesis appears normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 1		DOID:0060578	OMIM:163950	J:242312

Genotype
MGI:5469863

cn3

• Allelic Composition: Slc17a6^tm1.1Jder/Slc17a6^tm1.1Jder; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: B6.Cg-Emx1^tm1(cre)Krj Slc17a6^tm1.1Jder

nervous system

abnormal dendrite morphology ( J:192240 )

• adult CA1 hippocampal pyramidal neurons exhibit reduced dendritic arbor and reduced number of spines compared with control mice

abnormal dendritic spine morphology ( J:192240 )

• reduced number of spines in adult CA1 hippocampal pyramidal neurons exhibit

abnormal glutamate-mediated receptor currents ( J:192240 )

• young mice exhibit reduced evoked synaptic glutamatergic transmission in CA3-CA1 connections compared with control mice

reduced long-term depression ( J:192240 )

• in young CA3-CA1 connections

decreased synaptic glutamate release ( J:192240 )

• decreased evoked glutamate release probability

increased paired-pulse ratio ( J:192240 )

• increased paired-pulse ratio with decreased evoked release probability in young CA3-CA1 connections

behavior/neurological

increased exploration in new environment ( J:192240 )

abnormal spatial learning ( J:192240 )

• impaired spatial learning and memory in a Morris water maze

• however, treatment with D-Serine and D-amino acid oxidase inhibition enhances learning

abnormal spatial reference memory ( J:192240 )

• impaired spatial learning and memory in a Morris water maze

growth/size/body

decreased body size ( J:192240 )

• at P14 without a decrease in body weight

Genotype
MGI:6285755

cn4

• Allelic Composition: Glul^tm1.1Ncd/Glul^tm1.1Ncd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: B6.Cg-Glul^tm1.1Ncd Emx1^tm1(cre)Krj

mortality/aging

premature death ( J:272643 )

• increase in mortality after 3 weeks of age, with the highest mortality between 4 and 9 weeks and a survival ratio of about 70% at 9 weeks of age

behavior/neurological

decreased anxiety-related response ( J:272643 )

• fewer fecal boli are produced by mice during open field test sessions, suggesting reduced anxiety

abnormal locomotor activation ( J:272643 )

• 4-15 week old mice show alterations in locomotive activities in the open field test, with some mice being almost inactive while others show hypoactivity interrupted by bursts of sudden wild running

decreased vertical activity ( J:272643 )

decreased locomotor activity ( J:272643 )

• mice begin to exhibit hypoactivity at when subjected to mild stimulation such as removing the cage lid or gentle knocking on the cate at postnatal week 3

increased locomotor activity ( J:272643 )

• mice begin to exhibit periodic running fits when subjected to mild stimulation such as removing the cage lid or gentle knocking on the cate at postnatal week 3

seizures ( J:272643 )

• mice older than 6 weeks show facial automatisms with occasional falling and forelimb clonus, suggesting seizures

• intracranial EEG recordings of 4-28 week old mice indicate spontaneous recurrent seizures in 4 of 7 mice

• frequency, duration, and behavioral severity of seizures varies among mice, with a tendency of more frequent seizures with age, indicating the development of late-onset epileptic seizures

cardiovascular system

abnormal brain vasculature morphology ( J:272643 )

• blood vessels become dilated in the areas of the neocortex and of the hippocampus where neurodegeneration occurs

abnormal blood vessel physiology ( J:272643 )

• MRI cerebrovascular reactivity (the relative increase in blood oxygen level dependent signal during a carbon dioxide challenge) is reduced in neocortical areas in both 4 week and 12-15 week old mice indicating that cerebral blood vessels exhibit reduced ability to react to increases in carbon dioxide levels

• MRI cerebrovascular reactivity is reduced in the dorsal hippocampus at 4 weeks but not 12-15 weeks of age

homeostasis/metabolism

decreased aspartic acid level ( J:272643 )

• concentration of aspartate is lower in the cerebral cortex

• however, levels are normal in the cerebellum

decreased gamma-aminobutyric acid level ( J:272643 )

• concentration of GABA is lower in the cerebral cortex

• however, levels are normal in the cerebellum

decreased glutamic acid level ( J:272643 )

• concentration of glutamate is lower in the cerebral cortex

• however, levels are normal in the cerebellum

decreased glutamine level ( J:272643 )

• concentration of glutamine are lower in the cerebral cortex

• however, levels are normal in the cerebellum

nervous system

seizures ( J:272643 )

• mice older than 6 weeks show facial automatisms with occasional falling and forelimb clonus, suggesting seizures

• intracranial EEG recordings of 4-28 week old mice indicate spontaneous recurrent seizures in 4 of 7 mice

• frequency, duration, and behavioral severity of seizures varies among mice, with a tendency of more frequent seizures with age, indicating the development of late-onset epileptic seizures

abnormal brain vasculature morphology ( J:272643 )

• blood vessels become dilated in the areas of the neocortex and of the hippocampus where neurodegeneration occurs

hippocampus pyramidal cell degeneration ( J:272643 )

• with age, mice show selective degeneration of CA1 and CA3 pyramidal neurons

astrocytosis ( J:272643 )

• mice exhibit progressive astrogliosis with a significant increase at 4 weeks of age, prior to neuronal loss and epilepsy

• astrogliosis is first noted in astrocytes along cerebral blood vessels

neurodegeneration ( J:272643 )

• some mice show occasional focal lesions (small islands of neuronal loss) in the neocortex at 6 weeks of age

• with age, mice show selective degeneration of CA1 and CA3 pyramidal neurons and dentate granule cells which is apparent by 3 months of age

• the neocortex becomes progressively affected in multiple areas with age, particularly the retrosplenial, motor, somatosensory, parietal association and visual cortices, with neocortical neurodegeneration generally starting in the most superficial layer of the cortex

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
temporal lobe epilepsy		DOID:3328	OMIM:PS600512	J:272643

Genotype
MGI:5695285

cn5

• Allelic Composition: Magoh^{tm1c(KOMP)Dlsi}/Magoh⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: B6.Cg-Magoh^{tm1c(KOMP)Dlsi} Emx1^tm1(cre)Krj

nervous system

decreased brain size ( J:213515 )

• at P12, mutant mice exhibit significantly smaller brains than heterozygous Emx1^tm1(cre)Krj control mice

thin cerebral cortex ( J:213515 )

• at E16.5, cortical thickness is significantly reduced relative to wild-type controls, but thicker than in mice heterozygous for the Magoh^Mos2 allele (likely due to a contribution of ventrally derived neurons which migrate into the dorsal telencephalon, but are not targeted by Emx1-Cre)

Genotype
MGI:5817664

cn6

• Allelic Composition: Emx1^tm1(cre)Krj/?; Rai1^tm2.1Luo/Rai1^tm2.1Luo
• Genetic Background: either: (involves: 129S1/Sv * 129S2/SvPas * C57BL/6) or (involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6)

normal phenotype

no abnormal phenotype detected ( J:237687 )

• mice do not exhibit differences in behavior, motor function or body weight from controls

Genotype
MGI:5002699

cn7

• Allelic Composition: Pdcd10^tm1Wami/Pdcd10^tm1Wami; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129 * 129S2/SvPas * C57BL/6

mortality/aging

mortality/aging ( J:170480 )

N • mice exhibit normal survival to adulthood

nervous system

abnormal brain vasculature morphology ( J:170480 )

• 80% of mice 7 months or older develop vascular lesions in the forebrain unlike control mice

increased brain size ( J:170480 )

astrocytosis ( J:170480 )

• starting in early postnatal stages

neoplasm

increased hemangioma incidence ( J:170480 )

• 80% of mice 7 months or older develop vascular lesions in the forebrain unlike control mice

cardiovascular system

abnormal brain vasculature morphology ( J:170480 )

• 80% of mice 7 months or older develop vascular lesions in the forebrain unlike control mice

Genotype
MGI:6194753

cn8

• Allelic Composition: Celf4^tm1.1Frk/Celf4^tm1.1Frk; Emx1^tm1(cre)Krj/?
• Genetic Background: involves: 129 * C57BL/6J

behavior/neurological

increased susceptibility to induction of seizure by inducing agent ( J:19671 )

• seizure threshold measured by ECT test in this conditional null shows an increase in both males and females

nervous system

increased susceptibility to induction of seizure by inducing agent ( J:19671 )

• seizure threshold measured by ECT test in this conditional null shows an increase in both males and females

Genotype
MGI:3795740

cn9

• Allelic Composition: Celsr3^tm1Agof/Celsr3^tm2Agof; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

nervous system

abnormal anterior commissure morphology ( J:134879 )

• only diminutive bundles originating from the olfactory nuclei run caudally and turn but never cross the midline unlike in control mice (double heterozygotes)

abnormal brain internal capsule morphology ( J:134879 )

• subdural projections develop abnormally

• however, corticothalamic and thalamicortical axons are normal

abnormal corticospinal tract morphology ( J:134879 )

Genotype
MGI:3835560

cn10

• Allelic Composition: Nrg1^tm1Fej/Nrg1^tm1Fej; Emx1^tm1(cre)Krj/?
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

nervous system

nervous system phenotype ( J:145464 )

N • forebrain fully myelinated at 4 months of age

N • no morphological or biochemical differences from wild-type controls

Genotype
MGI:6710961

cn11

• Allelic Composition: Tor1a^tm2Wtd/Tor1a^tm3.1Wtd; Tor1b^tm1.2Wtd/Tor1b^tm1.2Wtd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

nervous system

thin cerebral cortex ( J:288753 )

• cortical thickness is normal at birth but is dramatically reduced by P28, with mice showing a nonsignificant reduction of CUX1+ (cortical layer II-IV) cortical neurons and a significant reduction of CTIP2+ (cortical layer V-VI) cortical neurons at P28

Genotype
MGI:5605975

cn12

• Allelic Composition: Tor1a^tm1Wtd/Tor1a^tm3.1Wtd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

behavior/neurological

limb grasping ( J:288753 )

• a subset of mice exhibit limb clasping during tail suspension

impaired coordination ( J:213785 )

• mice exhibit an increase in the number of footslip/cross in beam crossing

nervous system

thin cerebral cortex ( J:288753 )

• reduction in cortical thickness

• however, the number of CUX1+ (cortical layer II-IV) or CTIP2+ (cortical layer V-VI) cortical neurons is not altered

gliosis ( J:213785 )

• reactive gliosis is observed in corpus callosum

neurodegeneration ( J:213785 )

• observed in cortex

Genotype
MGI:6710955

cn13

• Allelic Composition: Tor1a^tm1Wtd/Tor1a^tm3.1Wtd; Tor1b^tm1.2Wtd/Tor1b^tm1.1Wtd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

mortality/aging

premature death ( J:288753 )

• mice exhibit early lethality beginning in the third postnatal week and endpoint of survival is P28

growth/size/body

postnatal growth retardation ( J:288753 )

• mice show reduced postnatal growth

nervous system

thin cerebral cortex ( J:288753 )

• cerebral cortex is thinner at P28, with a 64.8% reduction compared to 10.4% reduction in single conditional Tor1a homozygous mutant mice

• mice exhibit reductions of CUX1+ (cortical layer II-IV) and CTIP2+ (cortical layer V-VI) cortical neurons in sensorimotor cortex

• however, no overt brain structural abnormalities are seen at birth, cortical thickness is normal at birth, and the number of CTIP2+ (cortical layer V-VI) cortical neurons are not different at P0

gliosis ( J:288753 )

• mice exhibit gliosis in the cerebral cortex and hippocampus at P28

neurodegeneration ( J:288753 )

• mice exhibit cell loss in the cerebral cortex and hippocampus at P28

Genotype
MGI:6710956

cn14

• Allelic Composition: Tor1a^tm2Wtd/Tor1a^tm3.1Wtd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

nervous system

nervous system phenotype ( J:288753 )

N • cortical thickness is normal and mice have normal numbers of CUX1+ (cortical layer II-IV) and CTIP2+ (cortical layer V-VI) cells

Genotype
MGI:6710960

cn15

• Allelic Composition: Tor1a^tm2Wtd/Tor1a^tm3.1Wtd; Tor1b^tm1.2Wtd/Tor1b⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

behavior/neurological

limb grasping ( J:288753 )

• mice show increased limb clasping in the tail suspension test

nervous system

thin cerebral cortex ( J:288753 )

• cortical thickness is reduced

• however, CUX1+ (cortical layer II-IV) and CTIP2+ (cortical layer V-VI) cortical neuron counts are normal

Genotype
MGI:4430220

cn16

• Allelic Composition: Celsr1^tm1Fati/Celsr1^tm1Fati; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

integument

whorled hair ( J:157059 )

• a rosette-like pattern is seen on limbs, but no whorls develop on the body

Genotype
MGI:4459298

cn17

• Allelic Composition: Pals1^tm1Caw/Pals1^tm1Caw; Tsc2^tm1.1Mjg/Tsc2^tm1.1Mjg; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

nervous system

abnormal cerebral cortex morphology ( J:160624 )

• the medial cortex is partially restored compared to in Mpp5^tm1Caw/Mpp5^tm1Caw Emx1^tm1(cre)Krj/Emx1⁺ mice

Genotype
MGI:5538342

cn18

• Allelic Composition: Slc12a2^tm1.1Jheb/Slc12a2^tm1.1Jheb; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:201156 )

N • no behavioral abnormalities are detected

Genotype
MGI:5504444

cn19

• Allelic Composition: Pax6^tm2Pgr/Pax6^tm2Pgr; Smarcc2^tm1.1Stoy/Smarcc2^tm1.1Stoy; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

nervous system

abnormal neocortex morphology ( J:197141 )

• decreased cortical surface at P8

abnormal neuron number ( J:197141 )

• reduced of Cux1+ upper layer identity neurons

abnormal neuronal precursor cell number ( J:197141 )

• decreased Tbr2+ cells in E14.5 dorsal cortex

Genotype
MGI:5504443

cn20

• Allelic Composition: Pax6^tm2Pgr/Pax6^tm2Pgr; Smarcc2^tm1.1Stoy/Smarcc2⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

nervous system

nervous system phenotype ( J:197141 )

N • mice exhibit normal cortical surface at P8 and numbers of Tbr2+ intermediate progenitors at E14.5

abnormal neuron number ( J:197141 )

• mice exhibit increased production of Cux1+ upper layer identity neurons

Genotype
MGI:7518724

cn21

• Allelic Composition: Bptf^tm1.1Cwu/Bptf^tm1.1Cwu; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

mortality/aging

mortality/aging ( J:334252 )

N • mice are born in normal Mendelian ratios and survive to adulthood

growth/size/body

abnormal head shape ( J:334252 )

• mice exhibit an oddly shaped head at 9 months of age

decreased body weight ( J:334252 )

• mice show a significant reduction in body weight by P2; growth differences are maintained as mice grow older and are readily obvious by P10

• however, body weight is relatively normal at birth

craniofacial

abnormal head shape ( J:334252 )

• mice exhibit an oddly shaped head at 9 months of age

nervous system

increased neuron apoptosis ( J:334252 )

• at E15.5, but not at E13.5, mice show a 10-fold increase in the % of cleaved caspase 3-positive (CC3+) apoptotic cells within the intermediate zone (IZ) and cortical plate (CP) relative to control and heterozygous littermates; however, the % of apoptotic cells within the ventricular zone (VZ) is unaffected

• % of CC3+ cells remains elevated as late as P2, when it becomes accompanied by a similar 10-fold increase in Iba1+ microglia cells

abnormal neuronal precursor proliferation ( J:334252 )

• cortical progenitor cells show a 10% decrease in the fraction of cells exiting the cell cycle within a 24-h period, suggesting that cell cycle length is prolonged

• however, no blocks are noted in the cell cycle with normal cell proportions in the S- and M-phase relative to control samples

microgliosis ( J:334252 )

• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal

• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells

• frequency of Iba1+ cells remains significantly high at P7

decreased brain weight ( J:334252 )

• at birth (P0.5), mice show a significant reduction in brain weight resulting in a decreased brain weight to body weight ratio

decreased forebrain size ( J:334252 )

• at P12, mice show a massive reduction in forebrain size relative to control and heterozygous littermates

forebrain hypoplasia ( J:334252 )

• at P26, gross morphology of the hypoplastic forebrain is identical to that observed at P12, suggesting a developmental phenotype that does not worsen with age

abnormal cerebral cortex morphology ( J:334252 )

• mice exhibit severe cortical hypoplasia that is present from birth

abnormal stratification in cerebral cortex ( J:334252 )

• at P2, the proportion of superficial, late-born Satb2+ neurons (upper layers IIV) is reduced by 45% with fewer Satb2+ cells present in layer V and some Satb2+ cells located below layer VI; the proportion of deep, early-born Tbr1+ neurons (layer VI) is also significantly decreased

• Ctip2 immunostaining showed both lamination and cell fate defects: the proportion of Ctip2^high neurons in layer V is reduced >90%, while the proportion of Ctip2^low cells shows a 60% reduction in layer VI along with a 2.7-fold increase in layers IIIII

• immunostaining of Foxp1 (normally expressed in layers IV and V of the cortex) showed an overall decrease in the proportion of Foxp1+ cells, with most located within layer IV

decreased neuronal precursor cell number ( J:334252 )

• at E15.5, the % of Tbr2+/Hoechst+ intermediate progenitor cells (IPCs) is slightly but significantly decreased in forebrain sections

• however, radial glia progenitor cells (RGCs) show no reduction in cell number or any blocks in cell cycle progression that alter proliferation

abnormal neuron specification ( J:334252 )

• neuron fate specification defects include layer VI and layer II-IV neurons that maintain Ctip2 protein expression inappropriately, a massive decrease in Ctip2+ and Foxp1+ layer V neurons, and misplaced Satb2+ neurons residing below layer VI that likely never complete their migration to the upper layers

immune system

microgliosis ( J:334252 )

• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal

• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells

• frequency of Iba1+ cells remains significantly high at P7

cellular

increased neuron apoptosis ( J:334252 )

• at E15.5, but not at E13.5, mice show a 10-fold increase in the % of cleaved caspase 3-positive (CC3+) apoptotic cells within the intermediate zone (IZ) and cortical plate (CP) relative to control and heterozygous littermates; however, the % of apoptotic cells within the ventricular zone (VZ) is unaffected

• % of CC3+ cells remains elevated as late as P2, when it becomes accompanied by a similar 10-fold increase in Iba1+ microglia cells

abnormal neuronal precursor proliferation ( J:334252 )

• cortical progenitor cells show a 10% decrease in the fraction of cells exiting the cell cycle within a 24-h period, suggesting that cell cycle length is prolonged

• however, no blocks are noted in the cell cycle with normal cell proportions in the S- and M-phase relative to control samples

hematopoietic system

microgliosis ( J:334252 )

• at E15.5, but not at E13.5, mice exhibit more Iba1+ activated microglia within the ventricular zone (VZ) relative to control mice; however, levels of microglia within the intermediate zone (IZ) and cortical plate (CP) remain normal

• by P2, cortex shows a 10-fold increase in Iba1+ microglia cells relative to control and heterozygous samples, with a significantly higher incidence of Iba1+ CC3+ co-labeled cells

• frequency of Iba1+ cells remains significantly high at P7

behavior/neurological

behavior/neurological phenotype ( J:334252 )

N • adult mice show no differences in home cage behavior relative to control littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurodevelopmental disorder with dysmorphic facies and distal limb anomalies		DOID:0070514	OMIM:617755	J:334252

Genotype
MGI:5795755

cn22

• Allelic Composition: Pnkp^tm1.1Pmc/Pnkp^tm1.1Pmc; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

cellular

increased brain apoptosis ( J:226703 )

• loss of all dorsal telencephalic progenitors via apoptosis

decreased cell proliferation ( J:226703 )

• proliferation in the cortex is reduced by E15.5 compared with E13.5

growth/size/body

decreased body size ( J:226703 )

• body size is reduced at P5

nervous system

increased brain apoptosis ( J:226703 )

• loss of all dorsal telencephalic progenitors via apoptosis

decreased brain size ( J:226703 )

• brain size is reduced at P5

abnormal cerebellar cortex morphology ( J:226703 )

• almost complete absence of the cortex

Genotype
MGI:5504445

cn23

• Allelic Composition: Smarcc2^tm1.1Stoy/Smarcc2^tm1.1Stoy; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * C57BL/6

nervous system

abnormal neuron differentiation ( J:197141 )

• increase in indirect neurogenesis

• however, neuron migration and apoptosis are normal

abnormal neuronal precursor proliferation ( J:197141 )

• radial glial progenitors are biased to asymmetric nonneurogenic divisions and the production of intermediate progenitors instead of neurons

• however, proliferative capacity of intermediate progenitors is normal

abnormal neocortex morphology ( J:197141 )

• increased volume, surface area, anterior-posterior dimension and dorsoventral dimension

thickened cerebral cortex ( J:197141 )

• in the rostral, intermediate and caudal areas

abnormal neuronal precursor cell number ( J:197141 )

• twice as many nonapical pHH3+ (mitotic marker) cells in the cortex at E14.5

• increased Tbr2+ cells in the subventricular zone at E12.5 with progressive increase between E13.5 and E15.5

cellular

abnormal neuron differentiation ( J:197141 )

• increase in indirect neurogenesis

• however, neuron migration and apoptosis are normal

abnormal neuronal precursor proliferation ( J:197141 )

• radial glial progenitors are biased to asymmetric nonneurogenic divisions and the production of intermediate progenitors instead of neurons

• however, proliferative capacity of intermediate progenitors is normal

abnormal DNA methylation ( J:197141 )

• decreased CpG methylation on Cux1 and Tie1 promoters

Genotype
MGI:5504448

cn24

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Tg(CMV-GFP,-Smarcc2,-lacZ)#Stoy/0
• Genetic Background: involves: 129S2/SvPas

nervous system

abnormal neuron differentiation ( J:197141 )

• direct increase in neurogenesis

abnormal neocortex morphology ( J:197141 )

• decreased volume, surface area, anterior-posterior dimension and dorsoventral dimension

thin cerebral cortex ( J:197141 )

• thin cerebral cortex in the rostral, intermediate and caudal areas

• at P10, radial thickness is reduced that more severely affects the width of the upper layers and a slight increase in neuronal density at L6 compared with control mice

abnormal neuron number ( J:197141 )

• increase number of Tuj1+ neurons in the early cortical plate with subsequent decrease at E14.5 to E15.5

abnormal neuronal precursor cell number ( J:197141 )

• decreased Tbr2+ intermediate progenitor cells at E12.5 to E13

cellular

abnormal neuron differentiation ( J:197141 )

• direct increase in neurogenesis

abnormal DNA methylation ( J:197141 )

• increased CpG methylation on Cux1 and Tie1 promoters

Genotype
MGI:3616432

cn25

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Wnt3a^tm2Eag/Wnt3a⁺
• Genetic Background: involves: 129S2/SvPas

mortality/aging

postnatal lethality ( J:104373 )

• mice die shortly after birth

craniofacial

short mandible ( J:104373 )

• lower jaw is shorter than normal

nervous system

absent Cajal-Retzius cell ( J:104373 )

• at E12.5, the neocortical zone shows a near complete absence of Cajal-Retzius cells

• at !3.5 and 15.5. the band of Cajal-Retzius cells along the marginal zone of the cortex is absent

absent choroid plexus ( J:104373 )

• at E12.5, the choroid plexus is almost completely absent

abnormal cerebral cortex morphology ( J:104373 )

• at E10, the cortical hem is almost completely ablated

• the caudomedial cortex is highly disorganized and shrunken; however, at E18.5, the layers of the rostral cortex are correctly ordered

skeleton

short mandible ( J:104373 )

• lower jaw is shorter than normal

behavior/neurological

abnormal suckling behavior ( J:104373 )

• newborn mice are unable to suckle

Genotype
MGI:4442996

cn26

• Allelic Composition: Dact1^tm1.1Bnrc/Dact1^tm1.2Bnrc; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas

nervous system

nervous system phenotype ( J:159217 )

N • mice exhibit normal cellular organization and regional anatomy of the brain

abnormal dendritic spine morphology ( J:159217 )

• cultured hippocampal neurons exhibit reduced dendritic spine density, spine length, and spine head width compared with wild-type neurons

Genotype
MGI:4459295

cn27

• Allelic Composition: Pals1^tm1Caw/Pals1^tm1Caw; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas

mortality/aging

mortality/aging ( J:160624 )

N • mice exhibit normal survival

reproductive system

reproductive system phenotype ( J:160624 )

N • mice exhibit normal reproduction

nervous system

increased neuron apoptosis ( J:160624 )

• apoptosis in the cortex is increased beginning at E10.5 and peaks at E11 to E12 compared to in wild-type mice

premature neuronal precursor differentiation ( J:160624 )

• at E11 and E12, the number of postmitotic neurons is increased compared to in wild-type mice

• at E12, neuronal progenitor cells withdraw from the cell cycle 2.3-fold quicker than wild-type cells

abnormal neuronal precursor proliferation ( J:160624 )

• at E12 and E14, BrdU incorporation in neuronal progenitor cells is 2-fold less than in wild-type mice

• at E12.5 and E14.5, M-phase cell phospho-histone H3 labeling of neuronal progenitor cells is decreased compared to in wild-type mice

abnormal brain morphology ( J:160624 )

• mice exhibit fluid-filled cystic space contiguous with the lateral ventricle not observed in wild-type mice

abnormal cerebral cortex morphology ( J:160624 )

• the cerebral cortex is virtually absent compared to in wild-type mice

• at E12 and E14, cortical size and morphology is abnormal compared to in wild-type mice

loss of cortex neurons ( J:160624 )

thin cerebral cortex ( J:160624 )

• in the lateral cortex

behavior/neurological

behavior/neurological phenotype ( J:160624 )

N • mice exhibit normal reflexes and motor coordination

decreased exploration in new environment ( J:160624 )

• initiation of exploration in an open field is decreased compared to wild-type mice

abnormal spatial learning ( J:160624 )

• mice fail to locate a visible platform in a Morris water maze unlike wild-type mice

abnormal placing response ( J:160624 )

• mice fail the visual forepaw reach test unlike wild-type mice

jerky movement ( J:160624 )

jumpy ( J:160624 )

decreased grip strength ( J:160624 )

• mice perform poorly in a wire hang test compared with wild-type mice

abnormal gait ( J:160624 )

• mice exhibit irregular and jumpy movements that disrupt their stride and gait unlike wild-type mice

decreased locomotor activity ( J:160624 )

• in an open field

growth/size/body

decreased body weight ( J:160624 )

integument

disheveled coat ( J:160624 )

cellular

increased neuron apoptosis ( J:160624 )

• apoptosis in the cortex is increased beginning at E10.5 and peaks at E11 to E12 compared to in wild-type mice

premature neuronal precursor differentiation ( J:160624 )

• at E11 and E12, the number of postmitotic neurons is increased compared to in wild-type mice

• at E12, neuronal progenitor cells withdraw from the cell cycle 2.3-fold quicker than wild-type cells

abnormal neuronal precursor proliferation ( J:160624 )

• at E12 and E14, BrdU incorporation in neuronal progenitor cells is 2-fold less than in wild-type mice

• at E12.5 and E14.5, M-phase cell phospho-histone H3 labeling of neuronal progenitor cells is decreased compared to in wild-type mice

Genotype
MGI:4459297

cn28

• Allelic Composition: Pals1^tm1Caw/Pals1⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas

nervous system

premature neuronal precursor differentiation ( J:160624 )

• mice exhibit an intermediate phenotype compared with homozygous mice

abnormal neuronal precursor proliferation ( J:160624 )

• mice exhibit an intermediate phenotype compared with homozygous mice

small hippocampus ( J:160624 )

abnormal cerebral cortex morphology ( J:160624 )

• mice exhibit a small medial cerebral cortex compared with wild-type mice

• however, the lateral cortex is relatively spared

behavior/neurological

abnormal behavior ( J:160624 )

• mice exhibit an intermediate behavioral phenotype compared with homozygous mice

cellular

premature neuronal precursor differentiation ( J:160624 )

• mice exhibit an intermediate phenotype compared with homozygous mice

abnormal neuronal precursor proliferation ( J:160624 )

• mice exhibit an intermediate phenotype compared with homozygous mice

Genotype
MGI:4947981

cn29

• Allelic Composition: Orc3^tm1.1Zhua/Orc3^tm1.1Zhua; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas

nervous system

nervous system phenotype ( J:170581 )

N • mice exhibit normal number of Cajal-Retzius cells

N • mice exhibit normal cortical basement membrane

abnormal radial glial cell morphology ( J:170581 )

• at E14.5, mice exhibit severe disruption in the radial glial scaffold compared with wild-type mice

decreased radial glial cell number ( J:170581 )

• at E14.5, mice exhibit severe loss of radial glial cells compared with wild-type mice

decreased neuronal precursor proliferation ( J:170581 )

• at E13.5, mice exhibit reduced neural progenitor division, especially near the ventricular surface, compared with wild-type mice

cellular

abnormal radial glial cell morphology ( J:170581 )

• at E14.5, mice exhibit severe disruption in the radial glial scaffold compared with wild-type mice

decreased radial glial cell number ( J:170581 )

• at E14.5, mice exhibit severe loss of radial glial cells compared with wild-type mice

decreased neuronal precursor proliferation ( J:170581 )

• at E13.5, mice exhibit reduced neural progenitor division, especially near the ventricular surface, compared with wild-type mice

Genotype
MGI:5471312

cn30

• Allelic Composition: Sp2^tm1.1Htg/Sp2^tm1.1Htg; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas

mortality/aging

prenatal lethality, incomplete penetrance ( J:194076 )

• fewer than expected mice are recovered at birth

nervous system

abnormal neuron differentiation ( J:194076 )

• severely disrupted neuronal and glial differentiation

abnormal cortical plate morphology ( J:194076 )

• increased density at E14.5

abnormal cortical ventricular zone morphology ( J:194076 )

• disorganized at E14.5

abnormal embryonic/fetal subventricular zone morphology ( J:194076 )

• disorganized at E14.5

cellular

abnormal neuron differentiation ( J:194076 )

• severely disrupted neuronal and glial differentiation

Genotype
MGI:5302860

cn31

• Allelic Composition: Pomt2^tm1.1Hhu/Pomt2^tm1.1Hhu; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J

nervous system

abnormal radial glial cell morphology ( J:179356 )

• radial glial cells are disrupted during neocortical development

• radial glial cell processes extend beyond the disruptions of the pial basement membrane

abnormal forebrain morphology ( J:179356 )

• mice exhibit lamination defects with an indistinct layer I unlike in wild-type mice

• the two cerebral hemispheres are fused

• layers II/III, IV, V, and VI cannot be identified

abnormal Cajal-Retzius cell morphology ( J:179356 )

• Cajal-Retzius cells are disrupted during neocortical development

• unlike in wild-type mice, Cajal-Retzius cells are located between the diffuse cell zone and the cortical plate

• in some regions Cajal-Retzius cells are absent in some regions

abnormal Ammon gyrus morphology ( J:179356 )

• 2 mice exhibit lamination defects of pyramidal cells in all CA fields of the Ammon's horn with some pyramidal neurons displaced

abnormal hippocampus CA3 region morphology ( J:179356 )

• 10 of 13 mice exhibit dispersion of CA3 of the Ammon's horn with CA3 cells

abnormal dentate gyrus morphology ( J:179356 )

• wavy inferior blade

abnormal hippocampus layer morphology ( J:179356 )

• lamination defects

abnormal neocortex morphology ( J:179356 )

• mice exhibit ectopic fibroblasts in the upper half of the neocortex

astrocytosis ( J:179356 )

• in the upper half of the neocortex

cellular

abnormal radial glial cell morphology ( J:179356 )

• radial glial cells are disrupted during neocortical development

• radial glial cell processes extend beyond the disruptions of the pial basement membrane

abnormal basement membrane morphology ( J:179356 )

• the pial basement membrane and glia limitans are disrupted during development and in adult mice compared to in wild-type mice

Genotype
MGI:6192624

cn32

• Allelic Composition: Rem2^{tm1c(EUCOMM)Hmgu}/Rem2^{tm1c(EUCOMM)Hmgu}; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6N
• Cell Lines: HEPD0760_4_D07

nervous system

abnormal visual cortex morphology ( J:263600 )

• mice subjected to monocular deprivation exhibit reduced ocular dominance plasticity measured by optical imaging of intrinsic signals compared with control mice but to a lesser extent than in knock-out mice

Genotype
MGI:6358251

cn33

• Allelic Composition: Knl1^{tm1c(EUCOMM)Hmgu}/Knl1^{tm1c(EUCOMM)Hmgu}; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6N
• Cell Lines: HEPD0665_2_E05

nervous system

telencephalon hypoplasia ( J:278483 )

decreased neuron number ( J:278483 )

• in deep and upper layers

growth/size/body

microcephaly ( J:278483 )

• more severe than in mice with the conditional activated by Tg(GFAP-cre)25Mes

Genotype
MGI:5470140

cn34

• Allelic Composition: Zfp335^tm1.1Caw/Zfp335^tm1.1Caw; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6

nervous system

decreased brain size ( J:193339 )

loss of cortex neurons ( J:193339 )

• absent cortex lacking cortical neurons

Genotype
MGI:5470141

cn35

• Allelic Composition: Zfp335^tm1.1Caw/Zfp335⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6

nervous system

thin cerebral cortex ( J:193339 )

• modest reduction in size

Genotype
MGI:5315767

cn36

• Allelic Composition: Bhlhe22^tm2.1Meg/Bhlhe22^tm2.1Meg; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

nervous system

absent corpus callosum ( J:182304 )

absent hippocampal commissure ( J:182304 )

abnormal anterior corticospinal tract morphology ( J:182304 )

• mice exhibit a reduction of the corticospinal tract compared with wild-type mice

Genotype
MGI:5569795

cn37

• Allelic Composition: Islr2^tm1.1Ddg/Islr2^tm2.1Ddg; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * SJL

mortality/aging

premature death ( J:210221 )

• some mice die during the fourth postnatal week

nervous system

abnormal brain morphology ( J:210221 )

• hypoplastic thalamocortical projections

• few, if any, corticofugal and thalamocortical axons cross the pallial-subpallial boundary

• however, thalamocortical projections extension through the diencephalic-telencephalic boundary is normal

abnormal telencephalon development ( J:210221 )

• at P7, pallium and subpallium are almost completely disconnected

abnormal brain internal capsule morphology ( J:210221 )

• the main trunk is devoid of corticofugal axons

Genotype
MGI:6275610

cn38

• Allelic Composition: Atxn1^tm2Hzo/Atxn1^tm2Hzo; Atxn1l^tm2Hzo/Atxn1l^tm2Hzo; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd

behavior/neurological

impaired contextual conditioning behavior ( J:240674 )

• in a fear conditioning assay, mice exhibit reduced freezing, especially in the test of spatial context, indicating impaired learning and memory

• however, mice show normal social behavior in the three-chamber test

decreased anxiety-related response ( J:240674 )

• in the elevated plus-maze test, mice spend more time in the open arm and less in the closed arm, indicating reduced anxiety

increased locomotor activity ( J:240674 )

• mice cover a greater distance at a greater speed in the open-field test

nervous system

decreased dentate gyrus size ( J:240674 )

• the hippocampal dentate gyrus shows decreased thickness at 20 weeks of age, however the CA1 and CA3 regions are normal

decreased cerebral cortex cell number ( J:240674 )

• the number of CUX1+ neurons in layers 2-4 is reduced

• however, the corpus callosum appears normal

thin cerebral cortex ( J:240674 )

• mice show reduced thickness of cortical layers 2-4 at 5 and 20 weeks of age, whereas thickness of layers 5 and 6 remains normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
disease of mental health		DOID:150		J:240674

Genotype
MGI:5614429

cn39

• Allelic Composition: Epha4^tm1.1Bzh/Epha4^tm1.2Bzh; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd

behavior/neurological

behavior/neurological phenotype ( J:209606 )

N • unlike in germ line null mice, the gait is similar to that in wild-type mice

nervous system

abnormal corticospinal tract morphology ( J:209606 )

• increased midline re-crossing of axons dorsal to the central canal in both the cervical enlargement and lumbar spinal cord

Genotype
MGI:4947982

cn40

• Allelic Composition: Itgb1^tm1Mll/Itgb1^tm1Mll; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ

nervous system

nervous system phenotype ( J:170581 )

N

abnormal radial glial cell morphology ( J:170581 )

• radial glia processes in the cortical plate are wavy and frequently crisscross unlike in wild-type mice

• radial glia scaffold is disrupted prior to Cajal-Retzius displacement unlike in wild-type mice

• however, mice exhibit normal radial glia density and identity

radial glial endfoot detachment ( J:170581 )

• at E14.5, mice exhibit retraction of radial glia endfeet compared with wild-type mice

• at E15.0, radial glia endfoot retraction is more severe and spreads across the cortex unlike in wild-type mice

abnormal Cajal-Retzius cell morphology ( J:170581 )

• Cajal-Retzius cells are displaced deeper into the cortex than in wild-type mice

cellular

abnormal radial glial cell morphology ( J:170581 )

• radial glia processes in the cortical plate are wavy and frequently crisscross unlike in wild-type mice

• radial glia scaffold is disrupted prior to Cajal-Retzius displacement unlike in wild-type mice

• however, mice exhibit normal radial glia density and identity

radial glial endfoot detachment ( J:170581 )

• at E14.5, mice exhibit retraction of radial glia endfeet compared with wild-type mice

• at E15.0, radial glia endfoot retraction is more severe and spreads across the cortex unlike in wild-type mice

Genotype
MGI:7260161

cn41

• Allelic Composition: Adcy3^tm2.1Drs/Adcy3^tm2.1Drs; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ

behavior/neurological

abnormal object recognition memory ( J:281839 )

• in the novel object recognition test, mice do not recognize familiar objects as well as controls

abnormal response to new environment ( J:281839 )

• when feeding in a novel environment, mice are slower to feed than controls, indicating novelty-suppressed feeding

• however, mice show normal feeding in the home cage

impaired spatial learning ( J:281839 )

• in the Morris water maze, mice spend more time learning to identify the location of the hidden platform and do not recognize the previous location of the hidden platform as well as controls in the probe trial

abnormal long-term spatial reference memory ( J:281839 )

• in the Morris water maze, mice do not recognize the previous location of the hidden platform as well as controls in the probe trial

abnormal depression-related behavior ( J:281839 )

• mice exhibit a prodepression phenotype

behavioral despair ( J:281839 )

• mice exhibit longer periods of immobility in the tail-suspension test and in the forced swim test

hypoactivity ( J:281839 )

• mice are less active in home cages during the night time

• mice are less active and move a shorter distance in the open field test

• however, mice do not show reduced sociability or increased anxiety, spending similar time interacting with the target mouse as wild-type mice in the three-chamber sociability test and spending a similar period of time in the open arm as controls

Genotype
MGI:6393904

cn42

• Allelic Composition: Rnu11^tm1.1Rank/Rnu11^tm1.1Rank; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ

nervous system

decreased radial glial cell number ( J:266583 )

• significantly reduced number of RGCs in pallium of E13 and E14 embryos

• normal number of RGCs in pallium of E12 embryos

abnormal pallium development ( J:266583 )

• significantly thinner than wildtype in E14 embryos

• normal thickness in E13 embryos

absent hippocampus ( J:266583 )

decreased neuronal precursor cell number ( J:266583 )

• significantly reduced number of proliferating NPCs in pallium of E13 and E14 embryos

• significantly reduced number of intermediate progenitor cells (IPCs) in pallium of E13 and E14 embryos

• significantly reduced number of RGCs in pallium of E13 and E14 embryos

• normal number of proliferating NPCs in pallium of E12 embryos

• normal number of IPCs in pallium of E12 embryos

• normal number of RGCs in pallium of E12 embryos

decreased neuron number ( J:266583 )

• significantly reduced number of neurons in pallium of E14 embryos

• normal number of neurons in pallium of E12 and E13 embryos

cellular

increased cell death ( J:266583 )

• in pallium of E12-14 embryos

decreased radial glial cell number ( J:266583 )

• significantly reduced number of RGCs in pallium of E13 and E14 embryos

• normal number of RGCs in pallium of E12 embryos

growth/size/body

microcephaly ( J:266583 )

• owing to decrease in number of neuronal progenitor cells

Genotype
MGI:3582334

cn43

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Numb^tm1Ynj/Numb^tm1Ynj
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * CD-1

normal phenotype

no abnormal phenotype detected ( J:87149 )

• viable and fertile with no detectable phenotypes

Genotype
MGI:3582335

cn44

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Numb^tm1Ynj/Numb^tm1Ynj; Numbl^tm1Wmz/Numbl^tm1Wmz
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * CD-1

mortality/aging

postnatal lethality, incomplete penetrance ( J:87149 )

• animals that were small tended to die between P5 and P21

behavior/neurological

stereotypic behavior ( J:87149 )

• mutants that survived to adulthood appeared jittery

circling ( J:87149 )

• 25% of the mutants displayed circling behavior

social withdrawal ( J:87149 )

• mutants that survived to adulthood appeared to have normal life span but were solitary

sporadic seizures ( J:87149 )

• mutants that survived to adulthood exhibited sporadic seizures

growth/size/body

decreased body size ( J:87149 )

• most mutant mice were slightly smaller than controls but were within the normal range of sizes and survived to adulthood

• occasionally, they reached only about one-third the size of their littermates

nervous system

sporadic seizures ( J:87149 )

• mutants that survived to adulthood exhibited sporadic seizures

increased neuron apoptosis ( J:87149 )

• TUNEL staining of E14.5 embryonic brain sections suggest that increased cell death may contribute to the loss of mature neurons

abnormal neuron differentiation ( J:87149 )

• several experiments indicate that neural progenitor cell proliferation increased drastically in the mutant region

• starting from E10.5, Nestin-positive progenitor cells in the mutant showed very little radial organization

• mutant neural progenitor cells were organized into multiple clusters of neurogenic foci across the cortex and did not migrate to the outer layer of the cortex

abnormal embryonic neuroepithelium morphology ( J:87149 )

• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating

abnormal brain ventricle morphology ( J:87149 )

• rough ventricular surfaces in mutant brains are suggestive of the shedding of brain tissues into the ventricle; shed tissues were occasionally found in the lateral ventricles

enlarged brain ventricles ( J:87149 )

• extensive ventricular enlargement

abnormal forebrain morphology ( J:87149 )

• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating

• at E12.5, the forebrain exhibited undulating, folding, and invaginating with clumps of cells peeling into the lateral ventricle from the apical surface of the cortical ventricular zone

abnormal cortical marginal zone morphology ( J:87149 )

• marginal zone absent and displayed no discernible laminar structures

• contained numerous cell clusters

abnormal lateral ventricle morphology ( J:87149 )

• shed tissues were occasionally found in the lateral ventricles

absent corpus callosum ( J:87149 )

• no identifiable corpus callosum in the caudodorsal region while corpus callosum in the rostral region was relatively normal

small thalamus ( J:87149 )

• small thalamus

abnormal hippocampus morphology ( J:87149 )

abnormal cerebral cortex morphology ( J:87149 )

• overgrown caudodorsal neocortex and thinning of the lateral cortex

• in extreme cases, the caudodorsal region was nearly missing, with just a thin layer of the cortex remaining with extreme ventricular enlargement

• the volume of the mutant cortex was increased

abnormal neuron specification ( J:87149 )

• reduction in the number of mature neurons later in the double mutant animal was revealed by reduced expression of neuronal markers

ectopic cortical neuron ( J:87149 )

• multidendritic neurons, normally located in layer I, were distributed all over the mutant cortex

• Cajal-Retzius cells were displaced from the normal location in the outer layer of the neocortex to the ectopic sites across the cortex

reproductive system

female infertility ( J:87149 )

♀

male infertility ( J:87149 )

♂

hearing/vestibular/ear

abnormal hearing physiology ( J:87149 )

• 25% of the mutants displayed hypersensitivity to sound stimuli

embryo

abnormal embryonic neuroepithelium morphology ( J:87149 )

• by E10.5, the neuroepithelium in the dorsal forebrain was noticeably undulating

cellular

increased neuron apoptosis ( J:87149 )

• TUNEL staining of E14.5 embryonic brain sections suggest that increased cell death may contribute to the loss of mature neurons

abnormal neuron differentiation ( J:87149 )

• several experiments indicate that neural progenitor cell proliferation increased drastically in the mutant region

• starting from E10.5, Nestin-positive progenitor cells in the mutant showed very little radial organization

• mutant neural progenitor cells were organized into multiple clusters of neurogenic foci across the cortex and did not migrate to the outer layer of the cortex

Genotype
MGI:6331079

cn45

• Allelic Composition: Pik3r4^mbe/Pik3r4^tm1.1Mpnd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C3H/HeH * C57BL/6

nervous system

abnormal hippocampus pyramidal cell layer ( J:258027 )

• pyramidal cell layer is fractured

ectopic hippocampus pyramidal cells ( J:258027 )

• increase in the number of ectopic pyramidal cells in the stratum oriens layer

abnormal hippocampus stratum oriens morphology ( J:258027 )

• the stratum oriens layer contains ectopic pyramidal cells

Genotype
MGI:3760657

cn46

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Mycbp2^tm1Adia/Mycbp2^tm1Adia
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal axon guidance ( J:125702 )

• authors state that mice exhibit the same axonal guidance defects as observed in Phr1^tm1.1Adia homozygotes

• mice exhibit a track running through the internal capsule and retrogradely labeled cell bodies in the thalamus that is not observed in Phr1^tm1.1Adia homozygotes

• at E14.5 and E15.5, cortical axons fail to cross the corticostriatal boundary terminating in a bulb reminiscent of Probst bundle

• however, there is no delay in cortical axon outgrowth

enlarged lateral ventricles ( J:125702 )

• mice exhibit enlarged lateral ventricles

abnormal corpus callosum morphology ( J:125702 )

• collasal axons from the incipient visual cortex never cross into the corpus callosum as they do in wild-type mice, instead they extend anteriorly and medially to terminate in large bulbs known as Probst bundles

• descending corticofugal axons contribute to a thinner than normal corpus callosum

• however, corticofugal projections in the internal capsule do not contribute to the internal capsule

decreased corpus callosum size ( J:125702 )

• mice exhibit narrower corpus callosum comapred to in wild-type mice

abnormal hippocampus morphology ( J:125702 )

• hippocampal formations are reduced in size and dysmorphic compared to in wild-type mice

cellular

abnormal axon guidance ( J:125702 )

• authors state that mice exhibit the same axonal guidance defects as observed in Phr1^tm1.1Adia homozygotes

• mice exhibit a track running through the internal capsule and retrogradely labeled cell bodies in the thalamus that is not observed in Phr1^tm1.1Adia homozygotes

• at E14.5 and E15.5, cortical axons fail to cross the corticostriatal boundary terminating in a bulb reminiscent of Probst bundle

• however, there is no delay in cortical axon outgrowth

Genotype
MGI:6331087

cn47

• Allelic Composition: Pik3r4^tm1.1Mpnd/Pik3r4^tm1.1Mpnd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal hippocampus morphology ( J:258027 )

• the hippocampus is barely discernible, with no structured pyramidal cell layer or dentate gyrus at P0 and P11

• the severe, progressive degeneration of the hippocampus is associated with caspase-induced apoptosis

abnormal cerebral cortex morphology ( J:258027 )

• severe, progressive degeneration of the cortex that is associated with caspase-induced apoptosis

thin cerebral cortex ( J:258027 )

• reduction in cortical thickness at P0 that is more severe at P11

Genotype
MGI:5607737

cn48

• Allelic Composition: Emx1^tm1(cre)Krj/?; Kcnq2^tm1.1Avtz/Kcnq2^tm1.1Avtz
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:208109 )

• all mice die before P40

postnatal lethality, incomplete penetrance ( J:208109 )

• most mice die between P15 and P20

behavior/neurological

tonic-clonic seizures ( J:208109 )

• tonic-clonic seizure followed by premature death was seen in one mouse and unusual behaviors such as rearing, jumping, and falling are seen in the others, consistent with seizures

nervous system

tonic-clonic seizures ( J:208109 )

• tonic-clonic seizure followed by premature death was seen in one mouse and unusual behaviors such as rearing, jumping, and falling are seen in the others, consistent with seizures

abnormal hippocampus morphology ( J:208109 )

• hippocampal membrane fractions show reduced KCNQ3 protein levels by about 60% and KCNQ5 protein levels by about 40%

abnormal nervous system electrophysiology ( J:208109 )

• the M current is reduced by about 85%

• CA1 pyramidal neurons show a greater initial firing frequency and a greater final firing frequency, indicating elevated neuronal excitability

• CA1 pyramidal neurons show increased excitability seen as a more than 50% decreased medium afterhyperpolarization and a longer-lasting (2-fold increase) afterdepolarization

• pyramidal neurons fire first in bursts when the depolarization ramp surpasses spike threshold

abnormal action potential ( J:208109 )

• the threshold voltage for action potential generation is shifted to more depolarized membrane potentials, however, this is not accompanied by a decrease in action potential amplitude or in a decrease in the maximum rate of action potential activation

• pyramidal neurons are hyperexcitable, responding to current injections with an increased number and frequency of action potentials

• KCNQ allosteric activators, retigabine and ICA-27243, have only weak effects in pyramidal neurons compared to controls

abnormal afterhyperpolarization ( J:208109 )

• CA1 pyramidal neurons show a more than 50% reduction in medium afterhyperpolarization

abnormal brain wave pattern ( J:208109 )

• surface electrocorticography recordings of the cerebral cortex show episodes of polyspike events reaching to about 100 events within the first 15 min compared with hardly any events in controls

• polyspike events show multiple repetitive spikes typically followed by a wave of variable duration, indicating elevated cortical excitability

Genotype
MGI:5607738

cn49

• Allelic Composition: Emx1^tm1(cre)Krj/?; Kcnq3^tm1.1Avtz/Kcnq3^tm1.1Avtz
• Genetic Background: involves: 129S2/SvPas * C57BL/6

nervous system

abnormal hippocampus morphology ( J:208109 )

• hippocampal membrane fractions show reduced KCNQ2 protein levels by about 15% and KCNQ5 protein levels by about 20%

abnormal nervous system electrophysiology ( J:208109 )

• mice show a substantial loss of the M current, however the medium afterhyperpolarization is normal

• CA1 pyramidal neurons tend to show a smaller afterdepolarization, likely due to faster repolarization time course of the afterdepolarization

• KCNQ allosteric activators still markedly dampen neuronal excitability in pyramidal neurons as in controls

Genotype
MGI:6275604

cn50

• Allelic Composition: Cic^{tm1c(KOMP)Wtsi}/Cic^{tm1c(KOMP)Wtsi}; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6N

behavior/neurological

impaired contextual conditioning behavior ( J:240674 )

• in a fear conditioning assay, mice exhibit reduced freezing, especially in the test of spatial context, indicating impaired learning and memory

• however, mice show normal social behavior in the three-chamber test

decreased anxiety-related response ( J:240674 )

• in the elevated plus-maze test, mice spend more time in the open arm and less in the closed arm, indicating reduced anxiety

increased locomotor activity ( J:240674 )

• mice cover a greater distance at a greater speed in the open-field test

• mice treated with a low dose of amphetamine show reduced hyperactivity

nervous system

decreased dentate gyrus size ( J:240674 )

• the hippocampal dentate gyrus shows decreased thickness at 20 weeks of age, however the CA1 and CA3 regions are normal

abnormal cerebral cortex morphology ( J:240674 )

• mice exhibit a transient increase of apoptosis in the upper layers of the cortex at P5 that is no longer seen at P10

• however, the corpus callosum appears normal

decreased cerebral cortex cell number ( J:240674 )

• the number of CUX1+ neurons in layers 2-4 is reduced at 5 weeks

• numbers of CUX1+ and SATB2+ neurons in layers 2-4 of the cortex are normal at P0 but decline postnatally and by P10 are comparable to that at 5 weeks

• the numbers of progenitors and their proliferation rates in embryonic cortex are not different from wild-type

thin cerebral cortex ( J:240674 )

• mice show reduced thickness of cortical layers 2-4 at 5 and 20 weeks of age, whereas thickness of layers 5 and 6 remains normal

abnormal pyramidal neuron dendrite morphology ( J:240674 )

• layer 2/3 pyramidal neurons show reduced dendritic branching complexity in 5 week old mice

• however, layer 5 pyramidal neurons show normal dendritic branching

decreased neurotransmitter release ( J:240674 )

• mice show a decrease in the probability of presynaptic neurotransmitter release

• however, basal synaptic transmission and long-term synaptic plasticity are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
disease of mental health		DOID:150		J:240674

Genotype
MGI:3584257

cn51

• Allelic Composition: Bdnf^tm1Krj/Bdnf⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

growth/size/body

growth/size/body region phenotype ( J:84683 )

N • forebrain specific heterozygotes do not become obese unlike mice heterozygous for Bdnf^tm1Lfr

Genotype
MGI:7312047

cn52

• Allelic Composition: Ppp4r3a^em1Qili/Ppp4r3a^em1Qili; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:326388 )

N • mice exhibit normal spatial learning and memory skills

abnormal sucrose solution preference ( J:326388 )

• decreased sucrose preference

behavioral despair ( J:326388 )

• increased immobility time in a tail suspension test and open field test

increased anxiety-related response ( J:326388 )

• reduced exploration of open arms in an elevated plus maze

increased thigmotaxis ( J:326388 )

nervous system

decreased dendritic spine density ( J:326388 )

• in the hippocampus

abnormal miniature excitatory postsynaptic currents ( J:326388 )

• reduced frequency and amplitude

decreased neurotransmitter release ( J:326388 )

• decreased glutamate release

Genotype
MGI:7335202

cn53

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Magoh^{tm1c(KOMP)Dlsi}/Magoh⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

growth/size/body

microcephaly ( J:235650 )

• in P12 mice

Genotype
MGI:7335203

cn54

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Rbm8a^tm1Dlsi/Rbm8a⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

growth/size/body

microcephaly ( J:235650 )

• microcephaly in P12 mice

nervous system

abnormal cerebral cortex morphology ( J:235650 )

• brains are missing most of their pallium

decreased neuron number ( J:235650 )

• Cux1+ neurons (layer II/III) are nearly ablated

• Satb2+ superficial and some deep layer neurons are reduced

Genotype
MGI:5316226

cn55

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Topbp1^tm1Pmc/Topbp1^tm1Pmc
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

nervous system

abnormal cerebral cortex morphology ( J:181920 )

• extensive cortical ablation

Genotype
MGI:5316224

cn56

• Allelic Composition: Atr^tm2Bal/Atr^tm2Bal; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

nervous system

abnormal corpus callosum morphology ( J:181920 )

• decreased in size and cellularity

hippocampus hypoplasia ( J:181920 )

• reduced cellularity

abnormal cerebral cortex morphology ( J:181920 )

• moderate perturbation of cortical development

• reduced cellularity, particularly in layers IV-II

abnormal stratification in cerebral cortex ( J:181920 )

• decrease in layer demarcation, particularly in layers IV-II

Genotype
MGI:3584256

cn57

• Allelic Composition: Bdnf^tm1Krj/Bdnf^tm1Lfr; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

mortality/aging

premature death ( J:84683 )

nervous system

abnormal medium spiny neuron morphology ( J:96903 )

• the cross-sectional area of medium spiny neuron soma is reduced by 25% and the diameter of all portions of the dendritic tree is reduced by about 40% compared to wild-type mice with spine density reduced by 30-40% at every order of dendrite

decreased striatum size ( J:96903 )

• the striatal volume is reduced by 15% at P14 and by 33% and P35 and P120

abnormal hippocampus morphology ( J:96903 )

• hippocampal volume is reduced by 12% at 14 days of age however by 120 days of age no significant reduction in hippocampal volume is seen

abnormal cerebral cortex morphology ( J:96903 )

• cortical volume is reduced by 16% at P14, by about 25% at P35, and by 30% at P120

abnormal visual cortex morphology ( J:84683 )

• in layer II/III of the visual cortex soma area is normal at 2 weeks of age but reduced by 28% and 29% at 3 and 5 weeks of age, respectively; however the number of neurons is not significantly different compared to wild-type mice

• in layer II/III of the visual cortex basal dendrite branching is normal at 2 weeks of age, but reduced by 29% at 5 weeks of age with distal branches more severely affected than proximal branches

• in layer II/III of the visual cortex the number of primary dendrites is normal at 2 weeks of age but reduced by 19% and 36% at 3 and 5 weeks of age, respectively, compared to wild-type mice

thin cerebral cortex ( J:84683 )

• at 5 weeks of age the thickness of the somatosensory and visual cortex are reduced by 12% and 17%, respectively and a 22% increase in neuron density is seen in layer II/III of the visual cortex compared to wild-type mice

behavior/neurological

increased aggression ( J:84683 )

limb grasping ( J:96903 )

• all mutants display limb clasping by 120 days of age and clasping progresses with age from only hindlimbs to include hind and forlimbs; however no impairment od motor function is seen in the rotarod test

abnormal nest building behavior ( J:84683 )

growth/size/body

decreased body weight ( J:84683 )

• body weight is reduced at 3 and 5 weeks of age

obese ( J:84683 )

• a 35% increase in body mass is seen at 16 weeks of age

reproductive system

reduced fertility ( J:84683 )

vision/eye

delayed eyelid opening ( J:84683 )

• mutants open their eyes 1 day later

Genotype
MGI:6382122

cn58

• Allelic Composition: Eif4a3^tm1.1Dlsi/Eif4a3⁺; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

growth/size/body

microcephaly ( J:235650 )

• mice exhibit severe microcephaly, with an average 70% reduction in cortical area of whole mount brains at P12

nervous system

abnormal telencephalon development ( J:235650 )

• the dorsal telencephalon is largely absent at E14.5 and of the remaining dorsal telencephalon tissue, the cortex is extremely thinned and neurons are disorganized

decreased brain size ( J:235650 )

• smaller brain at E12.5

decreased forebrain size ( J:235650 )

• forebrain is smaller at E12.5

abnormal neocortex morphology ( J:235650 )

• extensive apoptosis is seen in neocortices at E11.5 and is present in both neurons and neural stem cells throughout the dorsal cortex

• mitotic index is increased in neocortices at E11.5

• Pax6+ neural stem cells are reduced in density in neocortices at E12.5 and the thickness of the TUJ1+ neuronal layer is increased

decreased neocortex size ( J:235650 )

• neocortices are smaller at E12.5 and are 30% thinner

absent telencephalon ( J:235650 )

• the dorsal telencephalon is largely absent at E14.5

abnormal neuronal stem cell morphology ( J:235650 )

• Pax6+ neural stem cells are reduced in density in neocortices at E12.5, indicating neural stem cell depletion

Genotype
MGI:5523193

cn59

• Allelic Composition: Nr2f1^tm2.1Mist/Nr2f1^tm2.1Mist; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

nervous system

nervous system phenotype ( J:127387 )

N • subplate cells differentiate normally

abnormal cerebral cortex morphology ( J:127387 )

• altered thalamocortical targeting

• massively expanded frontal areas, including motor

• altered areal output projections

• projection neurons in the parietal cortex adopt the identity of motor area-projection neurons rather than S1 identity

abnormal primary somatosensory cortex morphology ( J:127387 )

• the primary sensory areas (A1, S1 and V1) are reduced in size and positioned far caudally in the cortical hemisphere compared with wild-type mice

• primary sensory areas coarsely maintain their positions relative to one another along the mediolateral cortical axis but not the rostrocaudal axis

abnormal barrel cortex morphology ( J:127387 )

• reduced size and ectopically located

Genotype
MGI:5896655

cn60

• Allelic Composition: Brpf1^{tm1c(EUCOMM)Wtsi}/Brpf1^{tm1c(EUCOMM)Wtsi}; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * C57BL/6N
• Cell Lines: EPD0069_1_G06

mortality/aging

postnatal lethality, incomplete penetrance ( J:224155 , J:241490 )

• most pups die prior to weaning at P21 (J:224155)

• most mice die before weaning (J:241490)

• however, a minority of mice survive beyond weaning (J:241490)

prenatal lethality, incomplete penetrance ( J:241490 )

• slightly fewer than mice are born

nervous system

nervous system phenotype ( J:241490 )

N • mice exhibit normal cerebellum

abnormal radial glial cell morphology ( J:224155 )

• distribution of Gfap+ radial glial cells in the dentate gyrus is slightly disturbed at E16.5 but becomes moderately and completely disorganized at P0 and P10, respectively

decreased radial glial cell number ( J:224155 )

• significantly fewer Gfap+ radial glial cells are found in the granular cell layer of the dentate gyrus at P10

abnormal neuronal precursor cell migration ( J:224155 )

• at P10, Tbr2+ intermediate neuronal progenitors fail to translocate to the subgranular zone and the hilum of the dentate gyrus, with some of Tbr2+ progenitors remaining at the outer rim of the molecular cell layer

• only a few NeuroD1+ neuroblasts are present in the granular cell of the dentate gyrus at P10, and almost none is found in the subgranular zone at P24, indicating abnormal migration of NeuroD1+ neuroblasts

• cell cycle progression of the dentate migration stream is impaired at E15.5, most likely through the G1 phase

decreased neuronal precursor proliferation ( J:224155 , J:241490 )

• at P10 and P24, Ki67+ neuronal precursors are missing in the dentate gyrus, indicating a dramatic lack of proliferation in the subgranular zone (J:224155)

• at E15.5, the number of BrdU+ progenitors is normal in the dentate migration stream whereas the Ki67+ cycling cell population (at G1, S, G2 and M, but not G0) is significantly increased, thereby decreasing the ratio of S-phase (BrdU+) over proliferating (Ki67+) cells (J:224155)

thin cortical plate ( J:241490 )

• at E15.5

• thinner layers V to VI at P0

• immediately after birth

abnormal corpus callosum morphology ( J:224155 )

decreased corpus callosum size ( J:241490 )

• absence of ventral and dorsal but not middle transverse sections at P14 and P24, but not E17.5 with only caudal reduction at P0

abnormal hippocampus morphology ( J:224155 )

• at P19, the hippocampus exhibits abnormal axon and dendritic trees in the dentate gyrus as well as in the CA regions

• at P10, the hippocampus fissure is malformed

abnormal hippocampus development ( J:224155 )

• mice exhibit partial agenesis of the hippocampus

abnormal dentate gyrus morphology ( J:224155 )

• at P0, the suprapyramidal blade is underdeveloped, with one end remaining attached to the ventricular zone, whereas the infrapyramidal blade is missing in the developing dentate gyrus

• at P0, a much smaller population of Ctip2+ neurons is observed in the suprapyramidal blade

• at P19, fewer neurons are observed in the dentate gyrus

decreased dentate gyrus size ( J:224155 )

• mice exhibit dentate gyrus hypoplasia at E17.5 and P0

abnormal hippocampal mossy fiber morphology ( J:224155 )

• at P8, mossy fibers of the suprapyramidal bundles and dentate hilum are missing

abnormal hippocampus pyramidal cell layer ( J:224155 )

• at P10 and P24, the pyramidal layers of CA1 and CA3 are not as tightly packed as in control mice

abnormal hippocampus neuron morphology ( J:224155 )

• at P19, the hippocampus exhibits disorganized neurons with less robust dendritic trees

• at P24, FoxG1+ neurons are abnormally found in the CA3 field and are not as tightly packed in the CA1 field

abnormal hippocampus region morphology ( J:224155 )

• nuclear layers of CA1 and CA3 appear more diffusely packed than in control mice

abnormal hippocampus CA1 region morphology ( J:224155 )

• border between cornu ammonis 1 (CA1) and the subiculum is not clearly defined at P10 or P24

increased subiculum size ( J:224155 )

• subiculum is expanded at P10 and P24

abnormal neocortex morphology ( J:224155 , J:241490 )

• altered lamination observed as early as E14.5 (J:241490)

decreased neocortex size ( J:241490 )

• shorter rostral-caudal length and thinner than in control mice

abnormal neuronal stem cell morphology ( J:224155 )

• at P0, the population of Sox2+ neural stem cells is decreased in the dentate gyrus; no enrichment of Sox2+ neural stem cells is noted in the subgranular zone at P10 and P14, unlike in control mice

decreased neuronal precursor cell number ( J:224155 )

• fewer Dcx+ immature neurons are found in the subgranular zone of the dentate gyrus at P10 and P24

• only a few NeuroD1+ neuroblasts are present in the granular cell of the dentate gyrus at P10, and almost none is found in the subgranular zone at P24

behavior/neurological

abnormal behavior ( J:241490 )

• one surviving mouse exhibited impaired marble burying behavior

decreased food intake ( J:241490 )

limb grasping ( J:241490 )

abnormal nest building behavior ( J:241490 )

• impaired nest building

growth/size/body

decreased body size ( J:241490 )

• at P10, but not P5, and persisting beyond weaning

prenatal growth retardation ( J:241490 )

cellular

abnormal cell physiology ( J:240552 )

• reduced histone H3K23 acetylation in cortex extracts

abnormal cell cycle checkpoint function ( J:224155 )

• cell cycle progression of the dentate migration stream is impaired at E15.5, most likely through the G1 phase; defects at E15.5 are smaller than those at or after P10

• M phase of the cell cycle appears unaffected

abnormal radial glial cell morphology ( J:224155 )

• distribution of Gfap+ radial glial cells in the dentate gyrus is slightly disturbed at E16.5 but becomes moderately and completely disorganized at P0 and P10, respectively

decreased radial glial cell number ( J:224155 )

• significantly fewer Gfap+ radial glial cells are found in the granular cell layer of the dentate gyrus at P10

abnormal neuronal precursor cell migration ( J:224155 )

• at P10, Tbr2+ intermediate neuronal progenitors fail to translocate to the subgranular zone and the hilum of the dentate gyrus, with some of Tbr2+ progenitors remaining at the outer rim of the molecular cell layer

• only a few NeuroD1+ neuroblasts are present in the granular cell of the dentate gyrus at P10, and almost none is found in the subgranular zone at P24, indicating abnormal migration of NeuroD1+ neuroblasts

• cell cycle progression of the dentate migration stream is impaired at E15.5, most likely through the G1 phase

decreased neuronal precursor proliferation ( J:224155 , J:241490 )

• at P10 and P24, Ki67+ neuronal precursors are missing in the dentate gyrus, indicating a dramatic lack of proliferation in the subgranular zone (J:224155)

• at E15.5, the number of BrdU+ progenitors is normal in the dentate migration stream whereas the Ki67+ cycling cell population (at G1, S, G2 and M, but not G0) is significantly increased, thereby decreasing the ratio of S-phase (BrdU+) over proliferating (Ki67+) cells (J:224155)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
syndromic intellectual disability		DOID:0050888		J:240552

Genotype
MGI:5607285

cn61

• Allelic Composition: Afdn^{tm1c(EUCOMM)Hmgu}/Afdn^{tm1c(EUCOMM)Hmgu}; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * C57BL/6N

embryo

abnormal embryonic neuroepithelium morphology ( J:215584 )

• marker analysis indicates disruption of adherens junctions in neuroepithelial cells at E13.5

nervous system

abnormal radial glial cell morphology ( J:215584 )

• adherens junctions between radial glial cells are disrupted

increased radial glial cell number ( J:215584 )

• increase in the proliferation of and in the number of Pax6+ radial glial cells at E13.5

abnormal embryonic neuroepithelium morphology ( J:215584 )

• marker analysis indicates disruption of adherens junctions in neuroepithelial cells at E13.5

abnormal telencephalon development ( J:215584 )

• accumulations of neurons at the surface of the ventricle and below the intermediate zone in which they form rosette-like structures at E16.5

thin cortical plate ( J:215584 )

• at E16.5

abnormal cortical ventricular zone morphology ( J:215584 )

• structure of the ventricular zone is disorganized

increased brain size ( J:215584 )

• brain is larger at P25

abnormal hippocampus morphology ( J:215584 )

• hippocampal structure is less well organized

abnormal cerebral cortex morphology ( J:215584 )

• mice exhibit subcortical band heterotopia, also known as double cortex, a malformation in which heterotopic gray matter is interposed between zones of white matter

• the cortex contains a thin layer of cells near the meninges and a disorganized mass of cells heterotopically localized deeper within the cortex

abnormal neocortex morphology ( J:215584 )

• severe disorganization of the neocortex at P15

• the thickness of the developing neocortex is increased at E13.5 and the ventricular surface is disrupted and irregular

• the neocortex is severely disorganized and hyperplastic at E16.5

• proliferating cells (Pax6+ RGCs and Tbr2+ intermediate progenitors) are broadly distributed throughout the entire thickness of the nascent neocortex at E13.5 and E16.5 compared to being confined to ventricular zone (VZ) and subventricular zone (SVZ) of controls

• at E13.5, Tuj1+ neurons are distributed irregularly with some of them occupying positions within the VZ and SVZ

increased neocortex size ( J:215584 )

• at P15, the neocortex is increased in size

• the thickness of the developing neocortex is increased at E13.5

abnormal stratification in cerebral cortex ( J:215584 )

• some subtypes of cortical projection neurons are generated but their assembly into neocortical cell layers is perturbed

abnormal nervous system tract morphology ( J:215584 )

• massive perturbations in axonal tracts

increased neuronal precursor cell number ( J:215584 )

• proliferation of cortical progenitor cells is increased, with the number of Ki67+ cells increased at E13.5 by about 50% in the neocortex, with an approximately equal increase in the number of Pax6+ radial glial cells and Tbr2+ intermediate progenitors

ectopic neuron ( J:215584 )

• the cortex contains a disorganized mass of cells heterotopically localized deeper within the cortex

cellular

abnormal cell cycle ( J:215584 )

• cell cycle regulation of cortical progenitor cells is altered in embryos

abnormal radial glial cell morphology ( J:215584 )

• adherens junctions between radial glial cells are disrupted

increased radial glial cell number ( J:215584 )

• increase in the proliferation of and in the number of Pax6+ radial glial cells at E13.5

Genotype
MGI:6502664

cn62

• Allelic Composition: Cmtr1^{tm1b(EUCOMM)Hmgu}/Cmtr1^{tm1b(EUCOMM)Hmgu}; Emx1^tm1(cre)Krj/Emx1⁺; Tg(Thy1-YFP)HJrs/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * C57BL/6N * CBA

nervous system

decreased neocortex size ( J:300305 )

abnormal dendrite morphology ( J:300305 )

• reduced number of dendritic intersections at a given distance from the soma of cortical layer 5 neuro

immune system

abnormal susceptibility to Riboviria infection ( J:300305 )

• lack of inflammatory response in Japanese-encephalitis-infected neocortex

Genotype
MGI:5896662

cn63

• Allelic Composition: Kat6a^{tm1c(EUCOMM)Wtsi}/Kat6a^{tm1c(EUCOMM)Wtsi}; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J * C57BL/6N * CD-1
• Cell Lines: EPD0028_5_E11

normal phenotype

no abnormal phenotype detected ( J:224155 )

• mice appear normal and show no detectable brain defects, as revealed by Nissl staining

Genotype
MGI:5897782

cn64

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Rcor2^{tm1c(EUCOMM)Wtsi}/Rcor2^{tm1c(EUCOMM)Wtsi}
• Genetic Background: involves: 129S2/SvPas * C57BL/6N

nervous system

decreased brain size ( J:235702 )

thin cerebral cortex ( J:235702 )

• at E13.5 and E15.5

Genotype
MGI:5614424

cn65

• Allelic Composition: Chn1^tm1Ito/Chn1^tm1.1Ito; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6NSlc

behavior/neurological

behavior/neurological phenotype ( J:209606 )

N • unlike in germ line null mice, the gait is similar to that in wild-type mice

Genotype
MGI:4399056

cn66

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Lhx2^tm1.1Ddmo/Lhx2^tm1.2Ddmo
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

nervous system

abnormal telencephalon morphology ( J:154611 )

• the telencephalon exhibits abnormal patterning compared to in wild-type mice

abnormal neocortex morphology ( J:154611 )

• at P7, the cortices are half the size of the cortices in wild-type mice

• the neocortex is small with abnormal lamination patterns compared to in wild-type mice

• the lateral neocortex is replaced with an ectopic piriform cortex that is not a displaced endogenous piriform cortex but refated lateral neocortex cells

• the ectopic piriform cortex is 400% larger than the normal piriform cortex

• between E15.5 and P0 the endogenous piriform cortex disappears

• however, the neocortex is normal at E13.5

abnormal olfactory bulb morphology ( J:154611 )

• olfactory bulb projections continue beyond the ectopic piriform cortex and project into layer 1 through much of the neo cortex unlike in wild-type mice

abnormal olfactory cortex morphology ( J:154611 )

• the lateral neocortex is replaced with an ectopic piriform cortex that is not a displaced endogenous piriform cortex but refated lateral neocortex cells

• at P7, the piriform cortex is absent from its normal ventral position

• however, the piriform cortex is present at E13.5

telencephalon hypoplasia ( J:154611 )

Genotype
MGI:4399057

cn67

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Lhx2^tm1.1Ddmo/Lhx2^tm1.1Ddmo
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

nervous system

abnormal telencephalon morphology ( J:154611 )

• the telencephalon exhibits abnormal patterning compared to in wild-type mice

abnormal neocortex morphology ( J:154611 )

• at P7, the cortices are half the size of the cortices in wild-type mice

• the neocortex is small with abnormal lamination patterns compared to in wild-type mice

• the lateral neocortex is replaced with an ectopic piriform cortex that is not a displaced endogenous piriform cortex but refated lateral neocortex cells

• the ectopic piriform cortex is 400% larger than the normal piriform cortex

• between E15.5 and P0 the endogenous piriform cortex disappears

• however, the neocortex is normal at E13.5

abnormal olfactory bulb morphology ( J:154611 )

• olfactory bulb projections continue beyond the ectopic piriform cortex and project into layer 1 through much of the neo cortex unlike in wild-type mice

abnormal olfactory cortex morphology ( J:154611 )

• the lateral neocortex is replaced with an ectopic piriform cortex that is not a displaced endogenous piriform cortex but refated lateral neocortex cells

• at P7, the piriform cortex is absent from its normal ventral position

• however, the piriform cortex is present at E13.5

telencephalon hypoplasia ( J:154611 )

Genotype
MGI:5308068

cn68

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Esco2^tm1.1Ge/Esco2^tm1.1Ge
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

nervous system

increased neuron apoptosis ( J:180371 )

• of neuronal progenitor cells in the ventricular zone

abnormal neuronal precursor proliferation ( J:180371 )

• 2-fold increase in the number of mitotic cells at E11.25 in the neuroepithelium of the neocortex but not of the ganglionic eminence

abnormal embryonic neuroepithelium morphology ( J:180371 )

• nearly complete agenesis of the neocortical and hippocampal neuroepithelium at E12.5

abnormal hippocampus development ( J:180371 )

• reduced hippocampal primordium at E11.25

• nearly complete agenesis of the neocortical and hippocampal neuroepithelium at E12.5

absent hippocampus ( J:180371 )

• in adult mice

abnormal neocortex morphology ( J:180371 )

• nearly complete agenesis of the neocortical and hippocampal neuroepithelium at E12.5

• neuroepithelium at E12.5

• adult mice lack most of the cortex

embryo

abnormal embryonic neuroepithelium morphology ( J:180371 )

• nearly complete agenesis of the neocortical and hippocampal neuroepithelium at E12.5

cellular

increased neuron apoptosis ( J:180371 )

• of neuronal progenitor cells in the ventricular zone

abnormal neuronal precursor proliferation ( J:180371 )

• 2-fold increase in the number of mitotic cells at E11.25 in the neuroepithelium of the neocortex but not of the ganglionic eminence

growth/size/body

microcephaly ( J:180371 )

• severe

Genotype
MGI:5607288

cn69

• Allelic Composition: Cdh2^tm1Glr/Cdh2^tm1Glr; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

nervous system

abnormal radial glial cell morphology ( J:215584 )

• adherens junctions between radial glial cells are disrupted

abnormal cortical ventricular zone morphology ( J:215584 )

• localization of adherens junction proteins is perturbed in the ventricular zone of the developing dorsal telencephalon at E13.5

abnormal cerebral cortex morphology ( J:215584 )

• laminar structure of the cortex is disrupted

abnormal neocortex morphology ( J:215584 )

• Pax6+ radial glial cells and Tbr2+ progenitor cells and Tuj1+ neurons are distributed throughout the entire thickness of the neocortex and the distribution of cells is not homogenous, and numerous rosette-like structures are detected

thickened cerebral cortex ( J:215584 )

• cortex is severely hyperplastic by P13 and vastly increased in size

abnormal nervous system tract morphology ( J:215584 )

• massive disorganization of axonal tracts

increased neuronal precursor cell number ( J:215584 )

• massive increases in progenitor cell numbers and in their proliferation at E13.5

ectopic neuron ( J:215584 )

• massive heterotopia forms below a thin band of cells near the meninges

cellular

abnormal radial glial cell morphology ( J:215584 )

• adherens junctions between radial glial cells are disrupted

Genotype
MGI:4412088

cn70

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Gsx2^tm2.1Kc/Gsx2^tm2.1Kc; Tg(CAG-cat,-EGFP)1Rbns/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL

nervous system

abnormal olfactory bulb development ( J:154936 )

• mice exhibit respecification of olfactory bulb interneuron towards olfactory bulb projection neuron cell fate, as determined by marker expression

Genotype
MGI:4412086

cn71

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Gsx2^tm2.1Kc/Gsx2^tm2.1Kc
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

nervous system

abnormal neuron differentiation ( J:154936 )

• mice exhibit defects in olfactory bulb neurogenesis, as determined by marker expression

abnormal olfactory bulb morphology ( J:154936 )

• mice exhibit defects in olfactory bulb neurogenesis, as determined by marker expression

abnormal lateral ganglionic eminence morphology ( J:154936 )

• mice exhibit respecification of null areas in the dorsal portion of the lateral ganglionic eminence toward a pallial cell fate

cellular

abnormal neuron differentiation ( J:154936 )

• mice exhibit defects in olfactory bulb neurogenesis, as determined by marker expression

Genotype
MGI:5496787

cn72

• Allelic Composition: Tsc2^tm1.1Kcess/Tsc2^tm1.1Kcess; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S/Sv * C57BL/6J

mortality/aging

postnatal lethality, complete penetrance ( J:195049 )

• mice start dying at P4 with complete lethality at P21

• however, rapamycin treatment rescues lethality

growth/size/body

decreased body weight ( J:195049 )

• however, treatment with rapamycin restores body weight

postnatal growth retardation ( J:195049 )

• during the first few days after birth

behavior/neurological

environmentally induced seizures ( J:195049 )

• prior to death in many mice during routine handling

nervous system

environmentally induced seizures ( J:195049 )

• prior to death in many mice during routine handling

Genotype
MGI:6385155

cn73

• Allelic Composition: Gm30731^tm1.1Dalm/Gm30731^tm1.1Dalm; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6

nervous system

abnormal cerebral cortex morphology ( J:281278 )

• altered postnatal cortical lamination

abnormal neocortex morphology ( J:281278 )

increased neuron number ( J:281278 )

• of CTIP2+neurons in the cortical plate at E13.5

abnormal neuronal stem cell physiology ( J:281278 )

• reduced proliferation of ventricular zone cells at E13.5

• fewer neurons born at E15.5 and P14 in the cortex with reduced BrdU+;CUX1+ cells in the upper layers

Genotype
MGI:4440904

cn74

• Allelic Composition: Bhlhe22^tm2.1Meg/Bhlhe22^tm2.1Meg; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: 129/Sv * 129S2/SvPas

behavior/neurological

behavior/neurological phenotype ( J:158273 )

N • mice do not show skin lesions

integument

integument phenotype ( J:158273 )

N • mice do not show skin lesions to selective deletion in the dorsal telencephalon

Genotype
MGI:5810138

cn75

• Allelic Composition: Bicd2^tm1Hgrd/Bicd2^tm1Hgrd; Emx1^tm1(cre)Krj/Emx1⁺
• Genetic Background: involves: C57BL/6

Abnormally oriented axonal bundles coursing from the superficial lamina towards the capsula interna in neocortex of Bicd2^tm1Hgrd/Bicd2^tm1HgrdEmx1^tm1(cre)Krj/Emx1⁺ mice

nervous system

nervous system phenotype ( J:210236 )

N • mice survive to >8 weeks (when they are sacrificed) and do not develop hydrocephalus

abnormal neuronal migration ( J:210236 )

• immunofluorescence of neurofilament-M revealed abnormally oriented axonal bundles coursing from the superficial lamina towards the capsula interna in the neocortex

abnormal hippocampus layer morphology ( J:210236 )

• mice exhibit disrupted laminar organization in the hippocampus

abnormal stratification in cerebral cortex ( J:210236 )

• mice exhibit disrupted laminar organization in the cerebral cortex

cellular

abnormal neuronal migration ( J:210236 )

• immunofluorescence of neurofilament-M revealed abnormally oriented axonal bundles coursing from the superficial lamina towards the capsula interna in the neocortex

Genotype
MGI:5803996

cn76

• Allelic Composition: Emx1^tm1(cre)Krj/Emx1⁺; Rbm8a^tm1Dlsi/Rbm8a⁺
• Genetic Background: involves: C57BL/6J

growth/size/body

microcephaly ( J:221648 )

• severe microcephaly at P0 and P12

• microcephaly arises during embryogenesis between E11.5 and E12.5, with marked microcephaly noted by E14.5

nervous system

abnormal radial glial cell apoptosis ( J:221648 )

• at E12.5, ~7% of all Pax6+ radial glia undergo apoptosis

increased neuron apoptosis ( J:221648 )

• at E12.5, radial glia apoptosis is less extensive than neuronal apoptosis, with ~7% of all Pax6+ radial glia undergoing apoptosis versus 21% of all Tuj1+ neurons

increased forebrain apoptosis ( J:221648 )

• at E11.5, a slight increase in apoptosis is observed in dorsal neocortices relative to controls, as shown by cleaved-caspase3 (CC3) and TUNEL staining

• by E12.5, extensive apoptosis is detected throughout the thickness of the neocortex and is especially high in basal layers (cortical plate and subplate), where neurons reside following migration

abnormal radial glial cell morphology ( J:221648 )

• at E13.5, the remaining radial glia in the neocortex appear disorganized

decreased radial glial cell number ( J:221648 )

• although the number of Pax6+ radial glial cells is normal at E11.5, a 54% reduction in radial glia density in seen in the developing neocortex by E12.5

• in culture, primary dissociated cells from E12.5 dorsal neocortices show a 1.5-fold reduction in Pax6+ radial glia relative to controls; a 2-fold decrease in radial glia is noted at E13.5

impaired neuron differentiation ( J:221648 )

• neurogenesis defects affecting progenitor proliferation, progenitor and neuron number, and apoptosis

premature neuronal precursor differentiation ( J:221648 )

• in culture, primary dissociated cells from E11.5 dorsal neocortices show a significantly lower fraction of EdU+Ki67+ cycling progenitors relative to controls, indicating that a higher fraction of progenitors have exited the cell cycle

• increased cell-cycle exit is associated with a significantly higher fraction of EdU+Tuj1+, consistent with an increased neuron number

increased neuronal precursor proliferation ( J:221648 )

• significant increase in cortical progenitor proliferation at E11.5 relative to controls, as determined by phospho-histone3 (PH3) staining

abnormal telencephalon development ( J:221648 )

• by E14.5, the ventricle and dorsal telencephalon are severely reduced

decreased brain size ( J:221648 )

• brains are ~70% smaller at P12

small brain ventricles ( J:221648 )

• by E14.5

abnormal cerebral cortex morphology ( J:221648 )

• significant reduction in the dorsal surface area of the cortex at P12

decreased neocortex size ( J:221648 )

• markedly thinner neocortex by E13.5

• most of the neocortex is missing at P0

abnormal stratification in cerebral cortex ( J:221648 )

• severe cortical lamination defects including loss of virtually all upper layer neurons

• at P0, remaining neocortical tissue shows a significant reduction of both Cux1+ (layers II/III) and Foxp1+ (layers III-V) neurons relative to controls

• although the density of Tbr1+ (layer VI) neurons is not significantly reduced at P0, Tbr1+ neurons are improperly distributed throughout the cortical tissue

thin cerebral cortex ( J:221648 )

• although brains show normal cortical thickness in dorsal neocortices at E11.5, cortices are 21% thinner by E12.5

• by E13.5, dorsal cortices are 50% thinner than in control brains; seen in both dorsal and more lateral cortical regions

decreased neuronal precursor cell number ( J:221648 )

• at E13.5, the density of Tbr2+ intermediate progenitors in the developing neocortex is reduced by 87%

increased neuron number ( J:221648 )

• significant increase in Tbr1+ deep-layer neurons in the neocortex at E12.5 relative to controls

• in culture, primary dissociated cells from E12.5 dorsal neocortices show a 2.7-fold increase in Tuj1+ immature neurons relative to controls; a similar (2.5-fold) increase in neuron number is noted at E13.5

ectopic cortical neuron ( J:221648 )

• although the relative distribution of Tuj1+ immature neurons is normal at E11.5, the layer of Tuj1+ neurons in the developing neocortex is strikingly expanded by E12.5

• at E13.5, Tuj1+ neurons are detected throughout the thickness of the dorsal neocortex, indicating aberrant distribution of postmitotic neurons

cellular

abnormal radial glial cell apoptosis ( J:221648 )

• at E12.5, ~7% of all Pax6+ radial glia undergo apoptosis

increased neuron apoptosis ( J:221648 )

• at E12.5, radial glia apoptosis is less extensive than neuronal apoptosis, with ~7% of all Pax6+ radial glia undergoing apoptosis versus 21% of all Tuj1+ neurons

increased forebrain apoptosis ( J:221648 )

• at E11.5, a slight increase in apoptosis is observed in dorsal neocortices relative to controls, as shown by cleaved-caspase3 (CC3) and TUNEL staining

• by E12.5, extensive apoptosis is detected throughout the thickness of the neocortex and is especially high in basal layers (cortical plate and subplate), where neurons reside following migration

abnormal radial glial cell morphology ( J:221648 )

• at E13.5, the remaining radial glia in the neocortex appear disorganized

decreased radial glial cell number ( J:221648 )

• although the number of Pax6+ radial glial cells is normal at E11.5, a 54% reduction in radial glia density in seen in the developing neocortex by E12.5

• in culture, primary dissociated cells from E12.5 dorsal neocortices show a 1.5-fold reduction in Pax6+ radial glia relative to controls; a 2-fold decrease in radial glia is noted at E13.5

impaired neuron differentiation ( J:221648 )

• neurogenesis defects affecting progenitor proliferation, progenitor and neuron number, and apoptosis

premature neuronal precursor differentiation ( J:221648 )

• in culture, primary dissociated cells from E11.5 dorsal neocortices show a significantly lower fraction of EdU+Ki67+ cycling progenitors relative to controls, indicating that a higher fraction of progenitors have exited the cell cycle

• increased cell-cycle exit is associated with a significantly higher fraction of EdU+Tuj1+, consistent with an increased neuron number

increased neuronal precursor proliferation ( J:221648 )

• significant increase in cortical progenitor proliferation at E11.5 relative to controls, as determined by phospho-histone3 (PH3) staining