Phenotypes associated with this allele

• Allele Symbol: Foxg1^tm1(cre)Skm
• Allele Name: targeted mutation 1, Susan K McConnell
• Allele ID: MGI:1932522
• Summary: 60 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxg1^tm1(cre)Skm/Foxg1^tm1(cre)Skm	129(Cg)-Foxg1^tm1(cre)Skm/J	MGI:3581545
ht2	Foxg1^tm1(cre)Skm/Foxg1^+	129(Cg)-Foxg1^tm1(cre)Skm/J	MGI:3580339
ht3	Foxg1^tm1(cre)Skm/Foxg1^+	B6.129P2-Foxg1^tm1(cre)Skm	MGI:3767188
ht4	Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:5806112
ht5	Foxg1^tm1(cre)Skm/Foxg1^+	involves: C57BL/6 * CBA	MGI:3767191
cn6	Fgfr2^tm1Dor/Fgfr2^tm1Dor Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116893
cn7	Fgfr2^tm1Dor/Fgfr2^tm1Dor Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa	involves: 129	MGI:6116896
cn8	Fgfr2^tm1Dor/Fgfr2^tm1Dor Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa	involves: 129	MGI:6116895
cn9	Fgfr2^tm1Dor/Fgfr2^tm1Dor Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm6.1Jrt/Fgfr1^tm1Jpa	involves: 129	MGI:6116894
cn10	Fgfr2^tm1Dor/Fgfr2^+ Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116892
cn11	Fgfr2^tm1Dor/Fgfr2^tm1Dor Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116891
cn12	Bmp4^tm1Blh/Bmp4^tm4Blh Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * Black Swiss * C57BL/6 * SJL	MGI:3805980
cn13	Tbx1^tm2.1Bem/Tbx1^tm2.2Bem Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * C57BL/6J * SJL * Swiss Webster	MGI:3619802
cn14	Notch1^tm1Grid/Notch1^tm2Rko Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * C57BL/6J * Swiss Webster	MGI:3776429
cn15	Chd7^Gt(S20-7E1)Sor/Chd7^tm1.1Dmm Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * C57BL/6 * Swiss Webster	MGI:4835272
cn16	Chd7^tm1.1Dmm/Chd7^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * C57BL/6 * Swiss Webster	MGI:4835273
cn17	Celsr3^tm1Agof/Celsr3^tm2Agof Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3795739
cn18	Gt(ROSA)26Sor^tm1(RARA*)Soc/Gt(ROSA)26Sor^tm1(RARA*)Soc Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3795697
cn19	Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3654831
cn20	Pbx1^tm1Koss/Pbx1^tm1Koss Pbx3^tm1Mlc/Pbx3^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:5305924
cn21	Cdc42^tm1Yizh/Cdc42^tm1Yizh Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3693870
cn22	Foxg1^tm1(cre)Skm/Foxg1^+ Lrp2^tm1Tew/Lrp2^tm1Tew	involves: 129P2/OlaHsd	MGI:6199478
cn23	Fgf8^tm1.2Mrt/Fgf8^tm1.3Mrt Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3720595
cn24	Aifm1^tm2Pngr/Y Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3687280
cn25	Fgf8^tm1.1Mrt/Fgf8^tm1.4Mrt Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:3654834
cn26	Rhoa^tm1Yuyo/Rhoa^tm1Yuyo Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd	MGI:5004979
cn27	Ntf3^tm1Esm/Ntf3^tm1Esm Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv	MGI:2653845
cn28	Apaf1^Gt(IRESBetageo)XIX18Pgr/Apaf1^Gt(IRESBetageo)XIX18Pgr Aifm1^tm2Pngr/Y Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3687281
cn29	Sp8^tm1Smb/Sp8^tm2Smb Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:7437676
cn30	Gt(ROSA)26Sor^tm1(Cacna1c*)Red/Gt(ROSA)26Sor^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5508374
cn31	Slc12a2^tm1.1Jheb/Slc12a2^tm1.1Jheb Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5538347
cn32	Igs1^tm11(CAG-Bgeo,-Edn2)Nat/Igs1^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5544092
cn33	Notch2^tm3Grid/Notch2^tm3Grid Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:4361706
cn34	Jag1^tm1Grid/Jag1^tm2Grid Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:3693201
cn35	Olig2^tm1Qrlu/Olig2^tm1Qrlu Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3615303
cn36	Mafb^tm1.1Good/Mafb^tm1Jeng Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * SJL	MGI:5581686
cn37	Lmo4^tm1Gan/Lmo4^tm2.1Gan Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J	MGI:4421423
cn38	Bmp4^tm3Blh/Bmp4^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3811334
cn39	Bmp4^tm3Blh/Bmp4^tm3Blh Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:2661104
cn40	Chd7^tm1.1Dmm/Chd7^tm1.1Dmm Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:5807348
cn41	Pbx1^tm1Mlc/Pbx1^+ Wnt9b^tm1Amc/Wnt9b^tm1Amc Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129X1/SvJ	MGI:5305933
cn42	Actb^tm1.1Erv/Actb^tm1.1Erv Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:4882049
cn43	Lmo4^tm2.1Gan/Lmo4^tm2.1Gan Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J	MGI:4421425
cn44	Bmp2^tm1Brd/Bmp2^tm1.1Mis Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:4430833
cn45	Pbx1^tm1Koss/Pbx1^tm1Koss Pbx2^tm1Mlc/Pbx2^tm1Mlc Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S/Sv	MGI:5305923
cn46	Pbx1^tm1Koss/Pbx1^tm1Koss Pbx2^tm1Mlc/Pbx2^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S/Sv	MGI:5305855
cn47	Wnt9b^tm1Amc/Wnt9b^tm1Amc Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129X1/SvJ	MGI:5305932
cn48	Sp8^tm2.1Aman/Sp8^tm2.1Aman Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:4455199
cn49	Atrx^tm1Rjg/Y Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:3530074
cn50	Foxg1^tm1(cre)Skm/? Gt(ROSA)26Sor^em1(ptxA)Btar/?	involves: 129P2/OlaHsd * C57BL/6J	MGI:6163707
cn51	Dll1^tm1Mjo/Dll1^tm1Mjo Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:3624333
cn52	Gt(ROSA)26Sor^tm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor^+ Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5551750
cn53	Bptf^tm1.1Cwu/Bptf^tm1.1Cwu Foxg1^tm1(cre)Skm/?	involves: 129P2/OlaHsd-Hprt^b-m3 * 129S1/Sv-Oca2^+ Tyr^+ Kitl^+	MGI:6763182
cn54	Fgfr1^tm1Upir/Fgfr1^tm1.1Upir Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * ICR	MGI:3702998
cn55	Fgfr1^tm1Upir/Fgfr1^tm1Upir Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * ICR	MGI:3702999
cn56	Six3^tm3Gco/Six3^tm3Gco Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129S1/Sv * C57BL/6	MGI:3814903
cn57	Top2b^tm2Jcw/Top2b^tm2.1Jcw Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129S4/SvJae * 129S6/SvEvTac * 129X1/SvJ	MGI:3521928
cn58	Bsnd^tm1Tjj/Bsnd^tm1Tjj Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129/Sv * 129P2/OlaHsd * 129X1/SvJ * C57BL/6	MGI:3826853
cn59	Foxg1^tm1(cre)Skm/Foxg1^+ Frs2^tm1Fwan/Frs2^tm1Fwan Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129 * Swiss Webster	MGI:6116890
cx60	Smarca1^tm1.1Pick/Y Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S4/SvJae * CD-1	MGI:5427352

Genotype
MGI:3581545

hm1

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1^tm1(cre)Skm
• Genetic Background: 129(Cg)-Foxg1^tm1(cre)Skm/J

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

mortality/aging

perinatal lethality, complete penetrance ( J:62916 )

• homozygous mice die perinatally

Genotype
MGI:3580339

ht2

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: 129(Cg)-Foxg1^tm1(cre)Skm/J

normal phenotype

no abnormal phenotype detected ( J:62916 )

• heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities

Genotype
MGI:3767188

ht3

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: B6.129P2-Foxg1^tm1(cre)Skm

nervous system

decreased forebrain volume ( J:128207 )

• volume of prosencephalon is reduced by 23%

small thalamus ( J:128207 )

• in adult, volume of thalamus is reduced by 21.6%, however at postnatal day 4, volume is not reduced

• total number of cells is reduced in levels 1 and 2 of the ventrobasal complex

abnormal telencephalon morphology ( J:128207 )

decreased striatum size ( J:128207 )

• volume of striatum is reduced by 29.7%

abnormal cerebral hemisphere morphology ( J:128207 )

• length of the medio-lateral and midline anterior-posterior axes of the cerebral hemispheres is reduced

• reduction in dimensions of cerebral hemispheres is observed by postnatal day 4

• area of cortical sheet is reduced at postnatal day 8 and in adult brain

decreased hippocampus volume ( J:128207 )

• volume of hippocampus is reduced by 18.6%

abnormal cerebral cortex morphology ( J:128207 )

• volume of cerebral cortex is reduced by 40.7%

• radial domain of cerebral cortex is substantially disrupted, especially in supragranular layers

• thickness of supragranular layer is reduced by 41.4% although granular and infragranular layers are not reduced

decreased cerebral cortex pyramidal cell number ( J:128207 )

• numbers of large and medium sized neurons are reduced in superficial layers of cortex

thin cerebral cortex ( J:128207 )

• Background Sensitivity: thinning is observed only in C57BL/6 background, not in mixed C57BL/6 and CBA background

Genotype
MGI:5806112

ht4

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

vision/eye

abnormal visual evoked potential ( J:235875 )

• visually evoked potential amplitudes at low spatial frequency are strongly diminished

• however, no changes in general organization, architecture and pattern or lamination of retina are seen

decreased visual acuity ( J:235875 )

• cortical visual acuity is reduced at P30

nervous system

abnormal cerebral cortex pyramidal cell morphology ( J:235875 )

• decrease in spine density, but not spine length, in the basal dendrites of pyramidal cells (layer 2/3) in visual cortices

abnormal visual cortex morphology ( J:235875 )

• the visual cortex is thinner, with specific layer II-III and layer IV reduction

• increase in interneuron density and a reduction of parvalbumin-positive cell density in layers II-III and VI of the visual cortex

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rett syndrome		DOID:1206	OMIM:312750 OMIM:613454	J:235875

Genotype
MGI:3767191

ht5

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: C57BL/6 * CBA

nervous system

abnormal brain morphology ( J:128207 )

• Background Sensitivity: reduction in dimensions of cerebral hemispheres is observed by postnatal day 4, however, on the mixed background the substantial reductions reported in the C57BL/6J forebrain are not observed

Genotype
MGI:6116893

cn6

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

cellular

cellular phenotype ( J:242687 )

N • cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity

increased cell death ( J:242687 )

• according to TUNEL assay at E8.75

nervous system

absent telencephalon ( J:242687 )

• at E12.5

Genotype
MGI:6116896

cn7

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm3.1Sor/Fgfr1^tm1Jpa
• Genetic Background: involves: 129

craniofacial

frontonasal prominence hypoplasia ( J:242687 )

• at E12.5

nervous system

telencephalon hypoplasia ( J:242687 )

• reduction in size across A/P and D/V axes at E12.5

abnormal lateral ganglionic eminence morphology ( J:242687 )

• absent at E13.5 according to lack of Lhx8- and Nkx2-1-labeling of LGE region

abnormal medial ganglionic eminence morphology ( J:242687 )

• absent at E13.5 according to lack of Lhx8- and Nkx2-1-labeling of MGE region

vision/eye

microphthalmia ( J:242687 )

• at E12.5

Genotype
MGI:6116895

cn8

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa
• Genetic Background: involves: 129

craniofacial

frontonasal prominence hypoplasia ( J:242687 )

• at E12.5

nervous system

telencephalon hypoplasia ( J:242687 )

• reduction in size across A/P and D/V axes at E12.5

vision/eye

microphthalmia ( J:242687 )

• at E12.5

Genotype
MGI:6116894

cn9

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm6.1Jrt/Fgfr1^tm1Jpa
• Genetic Background: involves: 129

nervous system

nervous system phenotype ( J:242687 )

N • brain morphology at E12.5

Genotype
MGI:6116892

cn10

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2⁺; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

cellular

cellular phenotype ( J:242687 )

N • cell survival and cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity

nervous system

nervous system phenotype ( J:242687 )

N • brain morphology at E12.5

Genotype
MGI:6116891

cn11

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

nervous system

absent telencephalon ( J:242687 )

• at E12.5

Genotype
MGI:3805980

cn12

• Allelic Composition: Bmp4^tm1Blh/Bmp4^tm4Blh; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * Black Swiss * C57BL/6 * SJL

hearing/vestibular/ear

abnormal scala media morphology ( J:136636 )

• cochlear ducts show variability in length

abnormal semicircular canal morphology ( J:136636 )

• less severely affected embryos display truncation of lateral canals

abnormal semicircular canal ampulla morphology ( J:136636 )

• not discernible in most severely affected embryos at E13.5

absent semicircular canals ( J:136636 )

• not discernible in most severely affected embryos at E13.5

abnormal utricle morphology ( J:136636 )

• malformed in most severely affected embryos at E13.5

abnormal vestibular saccule morphology ( J:136636 )

• malformed in most severely affected embryos at E13.5

abnormal endolymphatic duct morphology ( J:136636 )

• intact endolymphatic duct only is evident in dorsal region of inner ear

Genotype
MGI:3619802

cn13

• Allelic Composition: Tbx1^tm2.1Bem/Tbx1^tm2.2Bem; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * C57BL/6J * SJL * Swiss Webster

mortality/aging

neonatal lethality, complete penetrance ( J:105980 , J:109536 )

• mice do not survive beyond the neonatal period (J:105980)

• mutants die between E18.5 and E20.5 with multiple defects of the pharyngeal apparatus (J:109536)

homeostasis/metabolism

skin edema ( J:105980 )

• at E17.5, mutants appear edematous

craniofacial

abnormal craniofacial bone morphology ( J:109536 )

• at E17.5, mutants display severe malformations of craniofacial bone structures

fusion of basioccipital and basisphenoid bone ( J:105980 , J:109536 )

• at E17.5, mutants display fused basisphenoid and basioccipital bones (J:109536)

temporal bone hypoplasia ( J:105980 )

absent zygomatic arch ( J:105980 )

• zygomatic arch is missing

hyoid bone hypoplasia ( J:105980 )

• hyoid bone is hypoplastic

short mandible ( J:105980 )

• mandible is shorter than in wild-type

absent middle ear ossicles ( J:105980 , J:109536 )

• middle ear is absent (J:105980)

• at E15.5-E17.5, middle ear ossicles do not start the condensation process and thus fail to develop (J:109536)

absent masseter muscle ( J:105980 )

• in conditional mutants, the masseter muscle is absent

absent pterygoid muscle ( J:105980 )

• in conditional mutants, pterygoid muscles are absent

cleft secondary palate ( J:105980 , J:109536 )

• observed at E17.5 (J:105980)

• at E17.5, mutants exhibit cleft palate (J:109536)

absent outer ear ( J:105980 , J:109536 )

• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)

hearing/vestibular/ear

absent middle ear ossicles ( J:105980 , J:109536 )

• middle ear is absent (J:105980)

• at E15.5-E17.5, middle ear ossicles do not start the condensation process and thus fail to develop (J:109536)

absent outer ear ( J:105980 , J:109536 )

• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)

abnormal middle ear development ( J:109536 )

• at E10.5, the pharyngeal endoderm fails to invaginate toward the surface endoderm to form the tubotympanic recess, resulting in disruption of middle ear development

small otic vesicle ( J:109536 )

• at E10.5 or later

otic vesicle hypoplasia ( J:109536 )

• early otic vesicle development is normal; however, the structure is slightly hypoplastic by E10.5 and appears cystic at E17.5

• in contrast, periotic mesenchyme development appears normal

absent cochlea ( J:109536 )

absent semicircular canals ( J:109536 )

absent inner ear vestibule ( J:109536 )

abnormal endolymphatic duct morphology ( J:109536 )

• at E17.5, mutants display a cystic endolymphatic duct

otic capsule hypoplasia ( J:109536 )

• at E17.5, the otic capsule is hypoplastic

absent inner ear ( J:109536 )

• at E17.5, mutants show complete aplasia of inner ear sensory organs

inner ear hypoplasia ( J:109536 )

• at E17.5, mutants exhibit severe hypoplasia of the inner ear, developing only a cystic OV and endolymphatic duct

absent tubotympanic recess ( J:109536 )

• at E10.5, the pharyngeal endoderm fails to invaginate toward the surface endoderm to form the tubotympanic recess

absent tympanic ring ( J:105980 , J:109536 )

• at E17.5, mutants lack tympanic rings (J:109536)

respiratory system

pharynx hypoplasia ( J:105980 )

• pharynx in conditional null embryos is hypoplastic, lacking distal arches; the first pouch appears to be hypoplastic

skeleton

abnormal craniofacial bone morphology ( J:109536 )

• at E17.5, mutants display severe malformations of craniofacial bone structures

fusion of basioccipital and basisphenoid bone ( J:105980 , J:109536 )

• at E17.5, mutants display fused basisphenoid and basioccipital bones (J:109536)

temporal bone hypoplasia ( J:105980 )

absent zygomatic arch ( J:105980 )

• zygomatic arch is missing

hyoid bone hypoplasia ( J:105980 )

• hyoid bone is hypoplastic

short mandible ( J:105980 )

• mandible is shorter than in wild-type

absent middle ear ossicles ( J:105980 , J:109536 )

• middle ear is absent (J:105980)

• at E15.5-E17.5, middle ear ossicles do not start the condensation process and thus fail to develop (J:109536)

cardiovascular system

abnormal aortic arch morphology ( J:105980 )

• all null mutants have aortic arch defects

retroesophageal right subclavian artery ( J:105980 )

• mutants have retroesophageal right subclavian artery

abnormal cardiac outflow tract development ( J:105980 )

• at E10.5 all conditional mutants display hypoplasia of the outflow tract

persistent truncus arteriosus ( J:105980 )

• all conditional null mutants have a single outflow tract

ventricular septal defect ( J:105980 )

• in mutants the left ventricle communicates with the right through a large VSD

endocrine/exocrine glands

absent parathyroid glands ( J:105980 )

athymia ( J:105980 )

small thyroid gland ( J:105980 )

• thyroid glands are smaller than wild-type and ectopically placed in conditional null embryos while conditional heterozygous embryos have ectopically placed thyroid glands

immune system

athymia ( J:105980 )

muscle

absent masseter muscle ( J:105980 )

• in conditional mutants, the masseter muscle is absent

absent pterygoid muscle ( J:105980 )

• in conditional mutants, pterygoid muscles are absent

hematopoietic system

athymia ( J:105980 )

digestive/alimentary system

cleft secondary palate ( J:105980 , J:109536 )

• observed at E17.5 (J:105980)

• at E17.5, mutants exhibit cleft palate (J:109536)

nervous system

abnormal vestibulocochlear ganglion morphology ( J:109536 )

• at E10.5, the otic vesicle is surrounded by an expanded cochleovestibular ganglion rudiment

• at E11.5, the cochleovestibular ganglion is duplicated around the otic vesicle anterior-posterior midline

embryo

abnormal pharyngeal pouch morphology ( J:109536 )

• at E10.5, the first pharyngeal pouch fails to outgrow, preventing middle ear bone condensations

integument

skin edema ( J:105980 )

• at E17.5, mutants appear edematous

growth/size/body

absent masseter muscle ( J:105980 )

• in conditional mutants, the masseter muscle is absent

absent pterygoid muscle ( J:105980 )

• in conditional mutants, pterygoid muscles are absent

cleft secondary palate ( J:105980 , J:109536 )

• observed at E17.5 (J:105980)

• at E17.5, mutants exhibit cleft palate (J:109536)

absent outer ear ( J:105980 , J:109536 )

• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:105980 , J:109536

Genotype
MGI:3776429

cn14

• Allelic Composition: Notch1^tm1Grid/Notch1^tm2Rko; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * C57BL/6J * Swiss Webster

hearing/vestibular/ear

increased cochlear inner hair cell number ( J:132241 )

• increases in inner hair cell number are more than in Dll1^tm1Gos/Dll1^tm2Gos Jag2^tm1Grid/Jag2^tm1Grid mice

decreased organ of Corti supporting cell number ( J:132241 )

• decreases in inner hair cell number are slightly than in Dll1^tm1Gos/Dll1^tm2Gos Jag2^tm1Grid/Jag2^tm1Grid mice or Dll1^tm1Gos Jag2^tm1Grid homozygotes

nervous system

increased cochlear inner hair cell number ( J:132241 )

• increases in inner hair cell number are more than in Dll1^tm1Gos/Dll1^tm2Gos Jag2^tm1Grid/Jag2^tm1Grid mice

Genotype
MGI:4835272

cn15

• Allelic Composition: Chd7^{Gt(S20-7E1)Sor}/Chd7^tm1.1Dmm; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * C57BL/6 * Swiss Webster

mortality/aging

neonatal lethality, complete penetrance ( J:164582 )

• die within 1 day of birth with no obvious milk in the stomach

hearing/vestibular/ear

abnormal ear development ( J:164582 )

• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion

abnormal cochlea morphology ( J:164582 )

• severe defects in cochlear structures

• severely hypoplastic

abnormal cochlear sensory epithelium morphology ( J:310063 )

• undulating appearance in the middle turn of the cochlea

increased cochlear outer hair cell number ( J:310063 )

• supernumerary rows of outer hair cells in the apical cochlea at P1

• occasional extra rows of outer hair cells n the middle turn

• basal turn also shows supernumerary hair cells

decreased cochlea coiling ( J:164582 )

• undercoiled with abnormal twisting at the apex

absent lateral semicircular canal ( J:164582 )

absent posterior semicircular canal ( J:164582 )

abnormal crista ampullaris morphology ( J:164582 )

• absent cristae

decreased superior semicircular canal size ( J:164582 )

• hypoplastic

abnormal inner ear vestibule morphology ( J:164582 )

• severe defects in vestibular structures

absent utricle ( J:164582 )

absent vestibular saccule ( J:164582 )

small endolymphatic duct ( J:164582 )

• hypoplastic

nervous system

abnormal neuronal precursor proliferation ( J:164582 )

• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion

increased cochlear outer hair cell number ( J:310063 )

• supernumerary rows of outer hair cells in the apical cochlea at P1

• occasional extra rows of outer hair cells n the middle turn

• basal turn also shows supernumerary hair cells

abnormal vestibulocochlear ganglion morphology ( J:164582 , J:310063 )

• about 1.5 fold smaller at E10.5-E12.5 compared to heterozygous and wild-type controls (J:164582)

• reduction in cellular proliferation at E10.5 in the vestibulocochlear ganglion (J:164582)

• neurites extending away from the hair cells show abnormal looping in the apex at P1 (J:310063)

• abnormal neuritic projections in the middle turn (J:310063)

• disorganized and misrouted neurites in the basal turn (J:310063)

abnormal neuronal precursor cell number ( J:164582 )

• severe reduction in the number of neuroblasts in the otic epithelium and vestibulocochlear ganglion at E9.5, E10.5 and E11.5

craniofacial

short snout ( J:164582 )

• at E12.5

vision/eye

ocular hypertelorism ( J:164582 )

• medially displaced eyes at E12.5

behavior/neurological

abnormal suckling behavior ( J:164582 )

• die within 1 day of birth with no obvious milk in the stomach

cellular

abnormal neuronal precursor proliferation ( J:164582 )

• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion

growth/size/body

short snout ( J:164582 )

• at E12.5

Genotype
MGI:4835273

cn16

• Allelic Composition: Chd7^tm1.1Dmm/Chd7⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * C57BL/6 * Swiss Webster

hearing/vestibular/ear

abnormal ear development ( J:164582 )

• decrease in the number of proliferating cells in the otic epithelium at E10.5

decreased lateral semicircular canal size ( J:164582 )

• truncated or hypoplastic

nervous system

abnormal vestibulocochlear ganglion morphology ( J:164582 )

• decrease in the number of proliferating cells at E9.5 but not at E10.5

Genotype
MGI:3795739

cn17

• Allelic Composition: Celsr3^tm1Agof/Celsr3^tm2Agof; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

absent anterior commissure ( J:134879 )

abnormal brain internal capsule morphology ( J:134879 )

• despite normal expression in the dorsal thalamus, the three components of the internal capsule (corticothalamic axons, thalamocortical axons and subcerebral projections) are abnormal

• unlike in control mice, no thalamic fibers turn towards the striatum

• however, corticothalamic axons grow towards the ventral telencephalon

abnormal corticospinal tract morphology ( J:134879 )

Genotype
MGI:3795697

cn18

• Allelic Composition: Gt(ROSA)26Sor^{tm1(RARA*)Soc}/Gt(ROSA)26Sor^{tm1(RARA*)Soc}; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

telencephalon hypoplasia ( J:135403 )

• at E10.5, mice exhibit a 15% decrease in cell proliferation in the dorsal telencephalic progenitors due to slowed cell cycle progression compared to in control mice

• at E10.5, apoptosis is increased 5-fold in the pallium and 4-fold in the subpallium compared to in control mice

abnormal medial ganglionic eminence morphology ( J:135403 )

• Nkx2.1+ progenitor cells in the medial ganglionic eminence are mispecified

Genotype
MGI:3654831

cn19

• Allelic Composition: Fgf8^tm1.3Mrt/Fgf8^tm1.4Mrt; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

increased neuron apoptosis ( J:111586 )

• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

cellular

increased neuron apoptosis ( J:111586 )

• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

Genotype
MGI:5305924

cn20

• Allelic Composition: Pbx1^tm1Koss/Pbx1^tm1Koss; Pbx3^tm1Mlc/Pbx3⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

craniofacial

cleft upper lip ( J:178316 )

• cleft lip and/or palate

cleft palate ( J:178316 )

• cleft lip and/or palate

digestive/alimentary system

cleft palate ( J:178316 )

• cleft lip and/or palate

growth/size/body

cleft upper lip ( J:178316 )

• cleft lip and/or palate

cleft palate ( J:178316 )

• cleft lip and/or palate

Genotype
MGI:3693870

cn21

• Allelic Composition: Cdc42^tm1Yizh/Cdc42^tm1Yizh; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:116100 )

• numbers of homozygotes starts to decline after E13.5

nervous system

abnormal embryonic neuroepithelium morphology ( J:116100 )

• mutant embryos display a much thicker neuroepithelium (NE) wall, and a lack of telencephalic vesicle enlargement in the developing forebrain at E10.5

• roof plate has thinner NE wall and lacked invagination of dorsal telencephalon

• apical-basal polarity of NE of developing forebrain is disrupted

abnormal telencephalon development ( J:116100 )

• at E12.5, telencephalon remains single chambered and clear distinction between cortical plate and ganglionic eminences is absent

• in E11.5 mutants, neural progenitors and postmitotic neurons are intermingled throughout NE but in wild-type brain, progenitors are mainly confined to ventricular surface of forebrain and postmitotic neurons are found along apical-basal NE axis

abnormal folding of telencephalic vesicles ( J:116100 )

• roof plate lacks invagination of dorsal telencephalon at E12.5

small embryonic telencephalon ( J:116100 )

• between E9.5-12.5, mutants do not exhibit enlargement of telencephalic vesicles in contrast to wild-type embryos

holoprosencephaly ( J:116100 )

vision/eye

abnormal eye development ( J:116100 )

• in E9.5-12.5 mutants, eye development is delayed compared to wild-type

embryo

abnormal embryonic neuroepithelium morphology ( J:116100 )

• mutant embryos display a much thicker neuroepithelium (NE) wall, and a lack of telencephalic vesicle enlargement in the developing forebrain at E10.5

• roof plate has thinner NE wall and lacked invagination of dorsal telencephalon

• apical-basal polarity of NE of developing forebrain is disrupted

Genotype
MGI:6199478

cn22

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1⁺; Lrp2^tm1Tew/Lrp2^tm1Tew
• Genetic Background: involves: 129P2/OlaHsd

vision/eye

increased retina apoptosis ( J:238249 )

• increase in cell death in the retina between P5 and P21 and cell death increases, especially in the ganglion cell layer, with age

abnormal eye morphology ( J:238249 )

• the retrobulbar space (the space between the eyeball and the orbit) is reduced

• excessive axial elongation and posterior pole degenerative changes in eyes

• chorioretinal atrophy in some cases

• myopic chorioretinopathy

abnormal placement of pupils ( J:238249 )

• anterior segment is generally normal although pupillary ectopia is occasionally seen

abnormal lens morphology ( J:238249 )

• the lens thickness increases during postnatal development as in wild-type eyes but is lower at P330 and P390

ocular hypotelorism ( J:238249 )

• shorter inter-ocular distance

macrophthalmia ( J:238249 )

• bilateral eye enlargement

• eyes are 30% and 40% longer at P60 and P180

abnormal posterior eye segment morphology ( J:238249 )

• posterior staphyloma is seen from P21 onward

• lengthening of the ocular axis is primarily due to continuous vitreal chamber enlargement

• the vitreous chamber depth of eyes increases dramatically at all ages studied

• however, the anterior chamber depth and corneal radius of curvature increases similarly to wild-type from P15 to P510

decreased retina ganglion cell number ( J:238249 )

• cell density in the ganglion cell layer is first decreased at P15

abnormal retina bipolar cell morphology ( J:238249 )

• bipolar cells exhibit atrophic dendrites and their connections with the retinal ganglion cells appear thicker

abnormal optic nerve morphology ( J:238249 )

• reduction in the number of axons in the optic nerve at P150

• the optic nerve diameter is slightly increased at P150

abnormal retina pigment epithelium morphology ( J:238249 )

• peripapillary atrophy of the pigment epithelium consistent with a peripapillary staphyloma, a trait of myopic retinopathy

abnormal retina pigmentation ( J:238249 )

• widespread pigment dispersion affects most of the retina

thin retina inner nuclear layer ( J:238249 )

• thickness of the inner nuclear layer is decreased more than in wild-type mice from P5 to P90

• progressive decrease in cell density in the inner nuclear from P5 onwards

thin retina inner plexiform layer ( J:238249 )

• significant reduction of the inner plexiform layer thickness from P7 onwards

thin retina outer nuclear layer ( J:238249 )

• thickness of the outer nuclear layer is decreased more than in wild-type mice from P5 to P90

• progressive decrease in cell density in the outer nuclear layer from P5 onwards

decreased total retina thickness ( J:238249 )

• retinal thinning from P15 onwards

abnormal sclera morphology ( J:238249 )

• collagen fibrils in sclera form fewer lamellae at P90 and P180 and appear disorganized

• within lamellae, the organization of collagen fibrils is perturbed, with fibrils coursing parallel to each other and large areas devoid of fibrils rather than interweaving as in controls

• collagen fibril density is lower in the sclera

• morphology of collagen fibrils is very heterogeneous and their contour is irregular with rectangular- rather than oval-shaped fibrils, mean cross-sectional diameter is increased and the frequency of collagen fibers with both smaller and wider mean cross-sectional diameter is increased, indicating scleral staphyloma

sclera thinning ( J:238249 )

• scleral thickness at P90 and P180 is thinner by 33% and 50%, respectively

abnormal intraocular pressure ( J:238249 )

• intraocular pressure is lower at P330 and P390 but normal at other times

high myopia ( J:238249 )

cellular

increased retina apoptosis ( J:238249 )

• increase in cell death in the retina between P5 and P21 and cell death increases, especially in the ganglion cell layer, with age

decreased cell proliferation ( J:238249 )

• reduction of the proliferation index is seen at P3 and P5 in the eyes

nervous system

absent corpus callosum ( J:238249 )

abnormal dendrite morphology ( J:238249 )

• bipolar cells exhibit atrophic dendrites

decreased retina ganglion cell number ( J:238249 )

• cell density in the ganglion cell layer is first decreased at P15

abnormal retina bipolar cell morphology ( J:238249 )

• bipolar cells exhibit atrophic dendrites and their connections with the retinal ganglion cells appear thicker

abnormal optic nerve morphology ( J:238249 )

• reduction in the number of axons in the optic nerve at P150

• the optic nerve diameter is slightly increased at P150

pigmentation

abnormal retina pigment epithelium morphology ( J:238249 )

• peripapillary atrophy of the pigment epithelium consistent with a peripapillary staphyloma, a trait of myopic retinopathy

abnormal retina pigmentation ( J:238249 )

• widespread pigment dispersion affects most of the retina

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
degenerative myopia		DOID:11829		J:238249

Genotype
MGI:3720595

cn23

• Allelic Composition: Fgf8^tm1.2Mrt/Fgf8^tm1.3Mrt; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

perinatal lethality, complete penetrance ( J:122378 )

• mutant mice die at birth due to defects in forebrain development

nervous system

abnormal forebrain development ( J:122378 )

• at birth, mutants exhibit lethal defects in forebrain development

• however, overall development of the inner ear and cochlea appeared normal

hearing/vestibular/ear

abnormal cochlear sensory epithelium morphology ( J:122378 )

• at E18.5, IHCs and OHCs appear to be in direct contact with each other in some cochlear sections

abnormal pillar cell morphology ( J:122378 )

• at E18.5, mutant mice show a significant reduction in the size and number of pillar cells (PCs) relative to control mice

abnormal pillar cell differentiation ( J:122378 )

• at E18.5, the distance between the lateral edge of the IHC and the medial edge of the first row OHC (a measure of the degree of PC development) is significantly decreased along the length of the cochlea

• at E18.5, PCs with weak or no lumenal projections are noted along the entire cochlear length with no region-specific variations

absent pillar cells ( J:122378 )

• at E18.5, pillar cells are missing or underdeveloped

abnormal patterning of the organ of Corti ( J:122378 )

• at E18.5, lumenal surface of the organ of Corti shows disruption of pillar cell growth and close approximation of IHCs to OHCs

• however, the overall structure of the epithelium and putative developing pillar cells are normal up to E15

cellular

abnormal pillar cell differentiation ( J:122378 )

• at E18.5, the distance between the lateral edge of the IHC and the medial edge of the first row OHC (a measure of the degree of PC development) is significantly decreased along the length of the cochlea

• at E18.5, PCs with weak or no lumenal projections are noted along the entire cochlear length with no region-specific variations

Genotype
MGI:3687280

cn24

• Allelic Composition: Aifm1^tm2Pngr/Y; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:112874 )

♂ • conditional mutants (males) die by E17

cellular

abnormal mitochondrial morphology ( J:112874 )

♂ • mitochondria in cultured neurites are short and fragmented

♂ • while morphology is restored by expression of anchored Pdcd8, mitochondrial length is increased compared to controls; cristae in mutant neurons are dilated and disorganized vs wild-type; cross-sectional distance of mitochondrial cristae is ~2.5-fold wider than wild-type; expression of anchored Pdcd8 reduces intercristae distance from 20 to 17 microns

decreased neuron apoptosis ( J:112874 )

♂ • cultured neurons transfected with a mitochondrially-anchored Pdcd8 show similar survival to wild-type neurons expressing GFP

♂ • after camptothecin treatment, neurons show increased survival vs wild-type over the first 12 hours (~45% loss vs ~55% in wild-type)

increased neuron apoptosis ( J:112874 )

♂ • there is a marked increase in cell death in postmitotic cell regions

abnormal mitochondrial physiology ( J:112874 )

♂ • membrane potential is hyperpolarized relative to wild-type cells

♂ • membrane potential hyperpolarization is restored to normal by expression of anchored Pdcd8

♂ • ATP production and oxygen consumption in cultured mutant neurons is restored by mitochondrially anchored Pdcd8

decreased mitochondrial fission ( J:112874 )

♂ • mutant neurites have few mitochondria vs wild-type

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:112874 )

♂ • expression of complex I respiratory chain complex is abrogated in mutants

nervous system

decreased neuron apoptosis ( J:112874 )

♂ • cultured neurons transfected with a mitochondrially-anchored Pdcd8 show similar survival to wild-type neurons expressing GFP

♂ • after camptothecin treatment, neurons show increased survival vs wild-type over the first 12 hours (~45% loss vs ~55% in wild-type)

increased neuron apoptosis ( J:112874 )

♂ • there is a marked increase in cell death in postmitotic cell regions

thin cerebral cortex ( J:112874 )

♂ • cortical thickness is reduced, mostly at the cortical plate (CP) and intermediate zone (IZ) and to lesser extent the subventricular zone (SVZ)

Genotype
MGI:3654834

cn25

• Allelic Composition: Fgf8^tm1.1Mrt/Fgf8^tm1.4Mrt; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

increased neuron apoptosis ( J:111586 )

• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

cellular

increased neuron apoptosis ( J:111586 )

• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

Genotype
MGI:5004979

cn26

• Allelic Composition: Rhoa^tm1Yuyo/Rhoa^tm1Yuyo; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

abnormal brain development ( J:172044 )

• the apical/ventricular surface is disorganized

exencephaly ( J:172044 )

• increasing incidence of exencephaly from E13.5 to E14.5

• exencephalic mass consists of greatly expanded neural progenitors

increased neuronal precursor cell number ( J:172044 )

• exencephalic mass consists of greatly expanded neural progenitors

Genotype
MGI:2653845

cn27

• Allelic Composition: Ntf3^tm1Esm/Ntf3^tm1Esm; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

vision/eye

abnormal vision ( J:81563 )

• impaired visual function indicated by the visual cliff avoidance test: mutants often cross the cliff edge without hesitation and show no preference for either side of the box

nervous system

decreased CNS synapse formation ( J:81563 )

• reduced thalamocortical synaptic interactions

abnormal nervous system tract morphology ( J:81563 )

• thalamthalamocortical projections are similar to controls at P0, but by P3, axonal bundles projecting from the thalamus through the cortical white matter are reducedcortical projections are similar to controls at P0, but by P3, thalamocortical projection is reduced

• reduction in the number of lateral geniculate nucleus projections to the visual cortex and anteroventral and laterodorsal nuclei projections to retrosplenial cortex

Genotype
MGI:3687281

cn28

• Allelic Composition: Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}; Aifm1^tm2Pngr/Y; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

cellular

decreased neuron apoptosis ( J:112874 )

♂ • neurons show increased survival vs wild-type after camptothecin treatment

♂ • neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment

♂ • expression of anchored Pdcd8 does not provide further protection from death to neurons

increased neuron apoptosis ( J:112874 )

♂ • cultured neurons show increased apoptosis reconstituted with wild-type Pdcd8 compared to control; mutant neurons expressing Pdcd8 with a nuclear exclusion sequence show cell death equivalent to control neurons expressing GFP

abnormal mitochondrial physiology ( J:112874 )

♂ • cultured neurons can maintain oxygen consumption after camptothecin treatment if anchored Pdcd8 is expressed

nervous system

decreased neuron apoptosis ( J:112874 )

♂ • neurons show increased survival vs wild-type after camptothecin treatment

♂ • neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment

♂ • expression of anchored Pdcd8 does not provide further protection from death to neurons

increased neuron apoptosis ( J:112874 )

♂ • cultured neurons show increased apoptosis reconstituted with wild-type Pdcd8 compared to control; mutant neurons expressing Pdcd8 with a nuclear exclusion sequence show cell death equivalent to control neurons expressing GFP

thickened cerebral cortex ( J:112874 )

♂ • cortex is thickened compared to Pdcd8 conditional embryos

Genotype
MGI:7437676

cn29

• Allelic Composition: Sp8^tm1Smb/Sp8^tm2Smb; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

craniofacial

abnormal face development ( J:200761 )

• all (13 of 13) mice exhibited truncation of anterior facial structures

cleft upper lip ( J:200761 )

• 5 of 13 mice exhibited cleft lip and/or palate

cleft palate ( J:200761 )

• 5 of 13 mice exhibited cleft lip and/or palate

midline facial cleft ( J:200761 )

• all (13 of 13) mice showed incomplete medial nasal prominence approximation along the facial midline, resulting in a facial midline cleft

nervous system

abnormal telencephalon morphology ( J:200761 )

• mice exhibited malformations of the telencephalon

exencephaly ( J:200761 )

• only 1 of 13 mice exhibited exencephaly

growth/size/body

abnormal face development ( J:200761 )

• all (13 of 13) mice exhibited truncation of anterior facial structures

cleft upper lip ( J:200761 )

• 5 of 13 mice exhibited cleft lip and/or palate

cleft palate ( J:200761 )

• 5 of 13 mice exhibited cleft lip and/or palate

midline facial cleft ( J:200761 )

• all (13 of 13) mice showed incomplete medial nasal prominence approximation along the facial midline, resulting in a facial midline cleft

digestive/alimentary system

cleft palate ( J:200761 )

• 5 of 13 mice exhibited cleft lip and/or palate

vision/eye

vision/eye phenotype ( J:200761 )

N • none of the 13 mice analyzed showed ocular hypertelorism

Genotype
MGI:5508374

cn30

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Cacna1c*)Red}/Gt(ROSA)26Sor⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

nervous system

abnormal neuron morphology ( J:199433 )

• fewer cortical neurons expressing Satb2

• however, the number of Foxp1 and total neuron numbers are normal

Genotype
MGI:5538347

cn31

• Allelic Composition: Slc12a2^tm1.1Jheb/Slc12a2^tm1.1Jheb; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

hyperactivity ( J:201156 )

circling ( J:201156 )

hearing/vestibular/ear

abnormal inner ear morphology ( J:201156 )

• collapse of the membranes of the vestibular compartments

collapsed Reissner membrane ( J:201156 )

abnormal crista ampullaris morphology ( J:201156 )

• cristae degeneration

utricular degeneration ( J:201156 )

vestibular saccular degeneration ( J:201156 )

Genotype
MGI:5544092

cn32

• Allelic Composition: Igs1^{tm11(CAG-Bgeo,-Edn2)Nat}/Igs1⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

Absence of vascular defects in the brains of embryonic day 18 Igs1^{tm11(CAG-Bgeo,-Edn2)Nat}/Igs1⁺ Foxg1^tm1(cre)Skm/Foxg1⁺

mortality/aging

postnatal lethality ( J:201133 )

• early postnatal lethality

craniofacial

cleft palate ( J:201133 )

vision/eye

failure of eyelid fusion ( J:201133 )

digestive/alimentary system

cleft palate ( J:201133 )

growth/size/body

cleft palate ( J:201133 )

Genotype
MGI:4361706

cn33

• Allelic Composition: Notch2^tm3Grid/Notch2^tm3Grid; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

mortality/aging

premature death ( J:130929 )

• nearly two-thirds do not survive to adulthood

• born in approximately Mendelian ratios (21%)

growth/size/body

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

decreased body weight ( J:130929 )

• no apparent weight difference at P0

• weigh 27% less than controls at 2.5 week old

• weigh 47% less than controls at 8-19 week old

nervous system

small pituitary gland ( J:130929 )

• significantly smaller pituitary in size

increased neuronal precursor cell number ( J:130929 )

• increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants

abnormal sensory neuron morphology ( J:130929 )

• disorganized olfactory sensory neurons

neuron degeneration ( J:130929 )

• does not occur during early postnatal life (P0-2.5weeks), but increase as the animal ages

• increased TUNEL-positive cells in the neuronal layer of the olfactory epithelium

abnormal nervous system physiology ( J:130929 )

• lower Glutathione S-transferase activity in mutant olfactory epithelia

increased neuron apoptosis ( J:130929 )

• increased TUNEL-positive cells in the neuronal layer of the olfactory epithelium

• does not occur during early postnatal life (P0-2.5weeks), but increase as the animal ages

taste/olfaction

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

cellular

increased apoptosis ( J:130929 )

• increased TUNEL-positive cells in the apical layer of the olfactory epithelium (0.3 cells/mm vs. 0/mm)

increased neuron apoptosis ( J:130929 )

• increased TUNEL-positive cells in the neuronal layer of the olfactory epithelium

• does not occur during early postnatal life (P0-2.5weeks), but increase as the animal ages

endocrine/exocrine glands

small pituitary gland ( J:130929 )

• significantly smaller pituitary in size

respiratory system

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

craniofacial

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

Genotype
MGI:3693201

cn34

• Allelic Composition: Jag1^tm1Grid/Jag1^tm2Grid; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:115783 )

• mutants survive through E18.5

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:115783 )

N • at E15.5, inner ear structures not associated with sensory formation such as endolymphatic duct and sac, and crus are not affected

abnormal cochlea morphology ( J:115783 )

• formation of prosensory domain is disrupted by E18.5

abnormal cochlear hair cell morphology ( J:115783 )

• severe hair cell patterning defects are observed at E18.5

• no clear formation of rows or distinction between inner and outer hair cells is observed in midbasal regions of the organ of Corti; hair cells form in patches

• at E16.5, patterns look similar to those at E18.5 with patches of hair cells in midbasal regions and absent hair cells in very basal regions

• in middle portion of cochlea, patterning of inner and sparse outer hair cells is abnormal

abnormal cochlear hair cell number ( J:115783 )

• in apical turn of cochlea, there are only two rows instead of four rows of hair cells

absent cochlear hair cells ( J:115783 )

• no hair cell formation is observed in basal turns of cochlea; at E18.5, hair cells and supporting cells are absent in very basal region of cochlea

abnormal cochlear outer hair cell morphology ( J:115783 )

• no outer hair cells or supporting Deiter's cells are present in apex of cochlea

absent tunnel of Corti ( J:115783 )

• at E18.5, tunnel of Corti is not apparent

decreased cochlea coiling ( J:115783 )

abnormal lateral semicircular canal morphology ( J:115783 )

• semicircular canals are mostly absent, with only a small portion of lateral semicircular canal present at E15.5

abnormal crista ampullaris morphology ( J:115783 )

• cristae and ampullae are missing or severely disrupted by E14.5 in homozygotes

abnormal superior semicircular canal morphology ( J:115783 )

• at E15.5, only a small portion of the anterior canal is present in homozygotes

absent semicircular canals ( J:115783 )

• at E15.5, semicircular canals are largely absent

abnormal utricular macula morphology ( J:115783 )

• structure is extremely small, with few differentiating hair cells; severe disruption of differentiation of utricular macula is observed

small utricle ( J:115783 )

• observed at E13.5

abnormal vestibular saccule morphology ( J:115783 )

• at E13.5, saccule appears misshapen

• at E18.5, saccule and macula are relatively normal, but entire saccular structure is shaped differently compared to controls

nervous system

abnormal cochlear hair cell morphology ( J:115783 )

• severe hair cell patterning defects are observed at E18.5

• no clear formation of rows or distinction between inner and outer hair cells is observed in midbasal regions of the organ of Corti; hair cells form in patches

• at E16.5, patterns look similar to those at E18.5 with patches of hair cells in midbasal regions and absent hair cells in very basal regions

• in middle portion of cochlea, patterning of inner and sparse outer hair cells is abnormal

abnormal cochlear hair cell number ( J:115783 )

• in apical turn of cochlea, there are only two rows instead of four rows of hair cells

absent cochlear hair cells ( J:115783 )

• no hair cell formation is observed in basal turns of cochlea; at E18.5, hair cells and supporting cells are absent in very basal region of cochlea

abnormal cochlear outer hair cell morphology ( J:115783 )

• no outer hair cells or supporting Deiter's cells are present in apex of cochlea

Genotype
MGI:3615303

cn35

• Allelic Composition: Olig2^tm1Qrlu/Olig2^tm1Qrlu; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

nervous system

abnormal myelination ( J:105071 )

• no myelination in dorsal cortex while myelination in ventral cortex is normal

Genotype
MGI:5581686

cn36

• Allelic Composition: Mafb^tm1.1Good/Mafb^tm1Jeng; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:207904 )

respiratory system

apnea ( J:207904 )

• central apnea

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:207904 )

N • inner ear develops normally

nervous system

nervous system phenotype ( J:207904 )

N • spiral ganglion neuron neurite organization is normal

Genotype
MGI:4421423

cn37

• Allelic Composition: Lmo4^tm1Gan/Lmo4^tm2.1Gan; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J

hearing/vestibular/ear

abnormal inner ear morphology ( J:156733 )

• at E15.5, mice exhibit vestibular defects observed in Lmo4^tm1Gan homozygotes

abnormal semicircular canal ampulla morphology ( J:156733 )

• at E15.5, mice lack anterior and posterior ampullae unlike in wild-type mice

absent semicircular canals ( J:156733 )

Genotype
MGI:3811334

cn38

• Allelic Composition: Bmp4^tm3Blh/Bmp4⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

prenatal lethality, incomplete penetrance ( J:83123 )

• fewer mice survive to birth than expected

Genotype
MGI:2661104

cn39

• Allelic Composition: Bmp4^tm3Blh/Bmp4^tm3Blh; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:83123 )

• all die between E12.5 and E14.5

• only necrotic embryos are found at E14.5

craniofacial

retrognathia ( J:83123 )

• recessed jaws

abnormal face development ( J:83123 )

abnormal snout morphology ( J:83123 )

• recessed snout

vision/eye

abnormal eye development ( J:83123 )

• severely deficient

nervous system

nervous system phenotype ( J:83123 )

N • despite Cre-mediated deletion in the telencephalon, no defects in telencephalic patterning or development are detected

skeleton

retrognathia ( J:83123 )

• recessed jaws

growth/size/body

abnormal face development ( J:83123 )

abnormal snout morphology ( J:83123 )

• recessed snout

Genotype
MGI:5807348

cn40

• Allelic Composition: Chd7^tm1.1Dmm/Chd7^tm1.1Dmm; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

vision/eye

abnormal lens development ( J:231044 )

• optic vesicle is present and appears normal at E9.5, however no progression toward formation of optic cup or lens structures is seen even as late as E12.5

absent optic cup ( J:231044 )

• optic vesicle is present and appears normal at E9.5, however no progression toward formation of optic cup or lens structures is seen even as late as E12.5

Genotype
MGI:5305933

cn41

• Allelic Composition: Pbx1^tm1Mlc/Pbx1⁺; Wnt9b^tm1Amc/Wnt9b^tm1Amc; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * 129X1/SvJ

craniofacial

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip in all mice

cleft palate ( J:178316 )

digestive/alimentary system

cleft palate ( J:178316 )

growth/size/body

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip in all mice

cleft palate ( J:178316 )

Genotype
MGI:4882049

cn42

• Allelic Composition: Actb^tm1.1Erv/Actb^tm1.1Erv; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:167543 )

• mice seldom survive to adulthood

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:167543 )

N • stereocilia are apparently normal at 2 days of age

N • stereocilia are still present at 21 days of age

Genotype
MGI:4421425

cn43

• Allelic Composition: Lmo4^tm2.1Gan/Lmo4^tm2.1Gan; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J

hearing/vestibular/ear

abnormal inner ear morphology ( J:156733 )

• at E15.5, mice exhibit vestibular defects observed in Lmo4^tm1Gan homozygotes

abnormal semicircular canal ampulla morphology ( J:156733 )

• at E15.5, mice lack anterior and posterior ampullae unlike in wild-type mice

absent semicircular canals ( J:156733 )

Genotype
MGI:4430833

cn44

• Allelic Composition: Bmp2^tm1Brd/Bmp2^tm1.1Mis; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:156945 )

N • no obvious abnormalities in cochlea morphology is observed

Genotype
MGI:5305923

cn45

• Allelic Composition: Pbx1^tm1Koss/Pbx1^tm1Koss; Pbx2^tm1Mlc/Pbx2^tm1Mlc; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv

craniofacial

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip

cellular

decreased apoptosis ( J:178316 )

• in the nasal epithelial at E10.75

growth/size/body

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip

Genotype
MGI:5305855

cn46

• Allelic Composition: Pbx1^tm1Koss/Pbx1^tm1Koss; Pbx2^tm1Mlc/Pbx2⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/Sv

mortality/aging

neonatal lethality, complete penetrance ( J:178316 )

craniofacial

abnormal maxillary shelf morphology ( J:178316 )

• abnormal maxillary palatal and palatine process

absent premaxilla ( J:178316 )

• the premaxillary process is absent

abnormal nasal capsule morphology ( J:178316 )

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip

cleft palate ( J:178316 )

respiratory system

abnormal nasal capsule morphology ( J:178316 )

digestive/alimentary system

abnormal maxillary shelf morphology ( J:178316 )

• abnormal maxillary palatal and palatine process

cleft palate ( J:178316 )

skeleton

abnormal maxillary shelf morphology ( J:178316 )

• abnormal maxillary palatal and palatine process

absent premaxilla ( J:178316 )

• the premaxillary process is absent

abnormal nasal capsule morphology ( J:178316 )

growth/size/body

abnormal maxillary shelf morphology ( J:178316 )

• abnormal maxillary palatal and palatine process

abnormal nasal capsule morphology ( J:178316 )

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip

cleft palate ( J:178316 )

Genotype
MGI:5305932

cn47

• Allelic Composition: Wnt9b^tm1Amc/Wnt9b^tm1Amc; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ

craniofacial

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip in all mice

cleft palate ( J:178316 )

digestive/alimentary system

cleft palate ( J:178316 )

growth/size/body

bilateral cleft upper lip ( J:178316 )

• bilateral cleft lip in all mice

cleft palate ( J:178316 )

Genotype
MGI:4455199

cn48

• Allelic Composition: Sp8^tm2.1Aman/Sp8^tm2.1Aman; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:160653 )

• mice die at birth

nervous system

increased neuron apoptosis ( J:160653 )

• between E10.5 and E18.5, post-mitotic neurons and neuronal progenitors exhibit an increase in apoptosis in the forebrain compared to in wild-type mice

abnormal neuronal precursor proliferation ( J:160653 )

• at E18.5, fewer BrdU+ cells are found within the upper cortical layers of the subventricular zone while more are detected in the superficial positions in the cortical plate compared to in wild-type mice

abnormal forebrain development ( J:160653 )

• at E12.5 and E15.5, mice lack the septum at the rostral level unlike wild-type mice

• mice exhibit dysgenesis of the olfactory bulb and septum, including an almost complete absence of the midline, compared with wild-type mice

• corticofugal fiber tracts do not cross the midline and instead form probst bundles and, caudally, neuronal fibers form bundles between the internal and external capsules

abnormal telencephalon development ( J:160653 )

• as determined by marker expression, dorsal ventral patterning of the medial telencephalon is altered compared to in wild-type mice

• as determined by marker expression, mice exhibit abnormal cortical arealization and thalamic innervation compared to in wild-type mice

• mice exhibit defective preplate splitting compared with wild-type mice

abnormal cortical plate morphology ( J:160653 )

• as determined by marker expression, mice exhibit abnormal cortical arealization and thalamic innervation compared to in wild-type mice

• as determined by marker expression, lower cortical layers are not correctly specified and upper cortical layer neurons are reduced compared to in wild-type mice

• mice exhibit misspecification in specific cortical neuron subtypes (Cux1+, Lhx2+, Rorb+, and Etv1+)

thin cortical plate ( J:160653 )

abnormal olfactory bulb development ( J:160653 )

• mice exhibit dysgenesis of the olfactory bulb and septum, including an almost complete absence of the midline, compared with wild-type mice

holoprosencephaly ( J:160653 )

• mild rostral

forebrain hypoplasia ( J:160653 )

abnormal lateral ventricle morphology ( J:160653 )

• the lateral ventricles are fused because of the complete disgenesis of the midline unlike in wild-type mice

abnormal brain internal capsule morphology ( J:160653 )

• aberrant bundles of Gap43+ fibers form within the internal capsule with some axons projecting ectopically towards the marginal zone and basal telencephalon unlike in wild-type mice

abnormal basal ganglion morphology ( J:160653 )

• basal ganglia consist of a single eminence with a barely discernable constriction between the lateral and medial ganglion eminence compared to in wild-type mice

telencephalon hypoplasia ( J:160653 )

• at E12.5

craniofacial

abnormal craniofacial morphology ( J:160653 )

• at midgestation

cellular

increased neuron apoptosis ( J:160653 )

• between E10.5 and E18.5, post-mitotic neurons and neuronal progenitors exhibit an increase in apoptosis in the forebrain compared to in wild-type mice

abnormal neuronal precursor proliferation ( J:160653 )

• at E18.5, fewer BrdU+ cells are found within the upper cortical layers of the subventricular zone while more are detected in the superficial positions in the cortical plate compared to in wild-type mice

Genotype
MGI:3530074

cn49

• Allelic Composition: Atrx^tm1Rjg/Y; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:95953 )

♂ • mutant males die within 24 - 48 hours of birth, with only 1 male surviving to 24 days of age

behavior/neurological

absent gastric milk in neonates ( J:95953 )

♂ • mutant males lack milk in their stomachs

abnormal suckling behavior ( J:95953 )

♂ • mutant males do not suckle well

growth/size/body

decreased birth body size ( J:95953 )

♂ • mutants are smaller at birth

nervous system

absent dentate gyrus ( J:95953 )

♂ • the dentate gyrus is replaced by a mass of disorganized cells

decreased hippocampus pyramidal cell number ( J:95953 )

♂ • reduced numbers of CA1 and CA3 pyramidal neurons are seen

loss of hippocampal neurons ( J:95953 )

♂ • the subiculum and hippocampus are reduced in size

loss of cortex neurons ( J:95953 )

♂ • the frontal cortex is reduced in size especially in the caudal-medial cortex and cell density is decreased in the cortex as a result of increased cell death and not a change in proliferation

♂ • cell numbers in the cortical plate are reduced by 20-30%

♂ • cell loss is not seen at E13.5 but is significant at E15.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
alpha thalassemia-X-linked intellectual disability syndrome		DOID:0110030	OMIM:301040	J:95953

Genotype
MGI:6163707

cn50

• Allelic Composition: Foxg1^tm1(cre)Skm/?; Gt(ROSA)26Sor^{em1(ptxA)Btar}/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

hearing/vestibular/ear

abnormal cochlear hair cell stereociliary bundle morphology ( J:236519 )

• at birth the apical hair cells show severe bundle misorientation

mortality/aging

neonatal lethality, complete penetrance ( J:236519 )

nervous system

abnormal cochlear hair cell stereociliary bundle morphology ( J:236519 )

• at birth the apical hair cells show severe bundle misorientation

Genotype
MGI:3624333

cn51

• Allelic Composition: Dll1^tm1Mjo/Dll1^tm1Mjo; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

hearing/vestibular/ear

abnormal cochlear hair cell morphology ( J:107414 )

• hair cells in Dll1 conditional knockouts differentiate prematurely and hair cells can be seen in the apex of the cochlea at E17.5, while none are visible in control littermates

increased cochlear inner hair cell number ( J:107414 )

• by E17.5 and the inner hair-cell row seems to have been duplicated in the apex

• in rhw middle and basal regions, there are increased numbers of inner hair cells

increased cochlear outer hair cell number ( J:107414 )

• in the apex, between 6 and 8 rows of outer hair cells have formed in the mutant by E17.5

• in rhw middle and basal regions, there is one extra row of outer hair cells

decreased cochlea coiling ( J:107414 )

• at E17.5, there are fewer turns in the cochlea in the mutant compared to wild-type and in mutants the cochlea has a shorter length with an extreme broadening of the sensory patch at the apex

abnormal utricular macula morphology ( J:107414 )

• the utricular macula is severely reduced or lost

abnormal vestibular saccular macula morphology ( J:107414 )

• the saccular macula is severely reduced or lost

nervous system

abnormal cochlear hair cell morphology ( J:107414 )

• hair cells in Dll1 conditional knockouts differentiate prematurely and hair cells can be seen in the apex of the cochlea at E17.5, while none are visible in control littermates

increased cochlear inner hair cell number ( J:107414 )

• by E17.5 and the inner hair-cell row seems to have been duplicated in the apex

• in rhw middle and basal regions, there are increased numbers of inner hair cells

increased cochlear outer hair cell number ( J:107414 )

• in the apex, between 6 and 8 rows of outer hair cells have formed in the mutant by E17.5

• in rhw middle and basal regions, there is one extra row of outer hair cells

Genotype
MGI:5551750

cn52

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}/Gt(ROSA)26Sor⁺; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

Thymic aplasia, nasal malformations, and eye, pharyngeal and ear defects in Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}/Gt(ROSA)26Sor⁺ Foxg1^tm1(cre)Skm/Foxg1⁺ mice and microcephaly, ocular and ear defects in Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}/Gt(ROSA)26Sor⁺ Tg(Pax2-cre)1Akg/0 mice

mortality/aging

perinatal lethality, complete penetrance ( J:204435 )

hearing/vestibular/ear

abnormal cochlea morphology ( J:204435 )

• hypoplastic to varying degrees, but enlarged in two instances

abnormal common crus morphology ( J:204435 )

• enlarged at E14.5

absent lateral semicircular canal ( J:204435 )

absent utricle ( J:204435 )

absent vestibular saccule ( J:204435 )

abnormal endolymphatic duct morphology ( J:204435 )

• enlarged at E14.5

nervous system

abnormal forebrain morphology ( J:204435 )

cochlear ganglion degeneration ( J:204435 )

abnormal geniculate ganglion morphology ( J:204435 )

• abnormal size and misguided projections

abnormal glossopharyngeal ganglion morphology ( J:204435 )

• abnormal size and misguided projections

abnormal trigeminal ganglion morphology ( J:204435 )

• abnormal size and misguided projections

abnormal vagus ganglion morphology ( J:204435 )

• abnormal size and misguided projections

vestibular ganglion degeneration ( J:204435 )

respiratory system

abnormal nasal placode morphology ( J:204435 )

vision/eye

abnormal optic vesicle formation ( J:204435 )

hematopoietic system

athymia ( J:204435 )

• thymic aplasia

craniofacial

abnormal frontonasal prominence morphology ( J:204435 )

abnormal nasal placode morphology ( J:204435 )

taste/olfaction

abnormal nasal placode morphology ( J:204435 )

immune system

athymia ( J:204435 )

• thymic aplasia

endocrine/exocrine glands

athymia ( J:204435 )

• thymic aplasia

Genotype
MGI:6763182

cn53

• Allelic Composition: Bptf^tm1.1Cwu/Bptf^tm1.1Cwu; Foxg1^tm1(cre)Skm/?
• Genetic Background: involves: 129P2/OlaHsd-Hprt^b-m3 * 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺

mortality/aging

perinatal lethality, complete penetrance ( J:217534 )

taste/olfaction

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

nervous system

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

growth/size/body

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

respiratory system

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

craniofacial

abnormal olfactory sensory neuron morphology ( J:217534 )

• at E18.5 compared with controls there is a dramatic decrease in olfactory receptor expression despite the expression of Gap43 and Ncam1, markers of immature olfactory sensory neurons, but markers of mature olfactory sensory neurons are also diminished

Genotype
MGI:3702998

cn54

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1.1Upir; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * ICR

mortality/aging

neonatal lethality, complete penetrance ( J:78879 )

• mutants die within 24 hrs after birth

hearing/vestibular/ear

abnormal cochlea morphology ( J:78879 )

• at birth, mutant cochleae are frequently slightly shorter than normal

• however, mutant otocysts appear morphologically normal at E10.5 and E11.5

• in addition, initiation of cochlear duct outgrowth from the otocyst is unaffected at E12.5

abnormal cochlear sensory epithelium morphology ( J:78879 )

• at birth, the sensory epithelium of the upper cochlear half is arranged in small sensory patches that mainly consist of IHCs and pillar supporting cells, while the lower cochlear half is less severely affected

• in contrast, the vestibular sensory epithelium remains unchanged

abnormal organ of Corti morphology ( J:78879 )

• at around birth, the organ of Corti is severely disrupted due to impaired production of precursor cells between E12 and E15, as shown by BrdU labeling

abnormal cochlear hair cell development ( J:78879 )

• at E16.5, mutants display no molecular signs of HC specification or differentiation in the gap regions found between sensory patches; OHCs are more severely affected

• at E16.5, the remaining HCs in the sensory patches appear to undergo normal differentiation

• at E18.5, most cochlear sections are devoid of HCs and the greater epithelial ridge is abnormally thin, due to reduced precursor cell proliferation in the ventral wall of the cochlear duct between E12 and E15.5

• apparently, the remaining precursors of the organ of Corti preferentially differentiate into IHCs and pillar cells

• no differences in precursor cell proliferation rate are observed in the dorsal, non-sensory wall of the cochlear duct

decreased cochlear hair cell number ( J:78879 )

• at P0, mutants show a 85% reduction in the total number of differentiating HCs relative to wild-type mice

absent cochlear outer hair cells ( J:78879 )

• at birth, only very low numbers of OHCs are formed, and these are located in lower cochlear half

increased cochlear inner hair cell number ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show doublet IHCs instead of a single continuous IHC row

abnormal orientation of inner hair cell stereociliary bundles ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show an accumulation of disorientated IHCs at the edges

absent organ of Corti supporting cells ( J:78879 )

• at birth, the sensory patches found in the upper cochlear half frequently show no signs of differentiation of supporting cells

nervous system

abnormal cochlear hair cell development ( J:78879 )

• at E16.5, mutants display no molecular signs of HC specification or differentiation in the gap regions found between sensory patches; OHCs are more severely affected

• at E16.5, the remaining HCs in the sensory patches appear to undergo normal differentiation

• at E18.5, most cochlear sections are devoid of HCs and the greater epithelial ridge is abnormally thin, due to reduced precursor cell proliferation in the ventral wall of the cochlear duct between E12 and E15.5

• apparently, the remaining precursors of the organ of Corti preferentially differentiate into IHCs and pillar cells

• no differences in precursor cell proliferation rate are observed in the dorsal, non-sensory wall of the cochlear duct

decreased cochlear hair cell number ( J:78879 )

• at P0, mutants show a 85% reduction in the total number of differentiating HCs relative to wild-type mice

absent cochlear outer hair cells ( J:78879 )

• at birth, only very low numbers of OHCs are formed, and these are located in lower cochlear half

increased cochlear inner hair cell number ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show doublet IHCs instead of a single continuous IHC row

abnormal orientation of inner hair cell stereociliary bundles ( J:78879 )

• at birth, the small sensory patches found in the upper cochlear half frequently show an accumulation of disorientated IHCs at the edges

Genotype
MGI:3702999

cn55

• Allelic Composition: Fgfr1^tm1Upir/Fgfr1^tm1Upir; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * ICR

mortality/aging

neonatal lethality, complete penetrance ( J:78879 )

• phenotype is stated to be comparable to that of mice that are compound heterozygous for Fgfr1^tm1.1Upir and Fgfr1^tm1Upir and also heterozygous for Foxg1^tm1(cre)Skm; however, no data are presented in J:78879

hearing/vestibular/ear

abnormal cochlear sensory epithelium morphology ( J:78879 )

abnormal organ of Corti morphology ( J:78879 )

Genotype
MGI:3814903

cn56

• Allelic Composition: Six3^tm3Gco/Six3^tm3Gco; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

nervous system

holoprosencephaly ( J:140315 )

• many display a phenotype typical of holoprosencephaly

• anterior diencephalon is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 2		DOID:0110872	OMIM:157170	J:140315

Genotype
MGI:3521928

cn57

• Allelic Composition: Top2b^tm2Jcw/Top2b^tm2.1Jcw; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * 129X1/SvJ

mortality/aging

neonatal lethality, complete penetrance ( J:94879 )

• died of respiratory failure within 30 min after birth, however decreased body size was not observed as in homozygous Top2b mutant mice

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:94879 )

• lack the vigor of wild-type newborns, however show some body movements upon tactile stimulation

respiratory system

atelectasis ( J:94879 )

respiratory failure ( J:94879 )

• collapsed lung alveoli in dead pups suggests respiratory failure

nervous system

abnormal hippocampus morphology ( J:94879 )

abnormal hippocampus granule cell layer ( J:94879 )

• ill-defined granule cell layer in the hippocampus

abnormal hippocampus pyramidal cell layer ( J:94879 )

• ill-defined pyramidal cell layer in the hippocampus

abnormal cerebral cortex morphology ( J:94879 )

• thinner cortex

small olfactory bulb ( J:94879 )

• less developed olfactory bulb

Genotype
MGI:3826853

cn58

• Allelic Composition: Bsnd^tm1Tjj/Bsnd^tm1Tjj; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * 129X1/SvJ * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:143314 )

• mice fail to survive until adulthood

homeostasis/metabolism

dehydration ( J:143314 )

• mice are moderately dehydrated

hearing/vestibular/ear

collapsed Reissner membrane ( J:143314 )

Genotype
MGI:6116890

cn59

• Allelic Composition: Foxg1^tm1(cre)Skm/Foxg1⁺; Frs2^tm1Fwan/Frs2^tm1Fwan; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129 * Swiss Webster

nervous system

nervous system phenotype ( J:242687 )

N • differentiating field of cortical GABAergic interneurons at E13.5 according to Shh and Lhx6 labeling

abnormal cortical ventricular zone morphology ( J:242687 )

• reduced size of Dlx2-labeled region at E13.5

telencephalon hypoplasia ( J:242687 )

• reduction in size across A/P (-24%) and D/V (-16%) axes at E13.5

abnormal embryonic/fetal subventricular zone morphology ( J:242687 )

• reduced cell division at E13.5 according to mitotic marker p-HH3 immunoreactivity

abnormal lateral ganglionic eminence morphology ( J:242687 )

• reduction in subset of dopaminergic olfactory interneuron progenitors in dorsal LGE at E13.5 according to Pax6 labeling

abnormal medial ganglionic eminence morphology ( J:242687 )

• reduced size of Nkx2-1-labeled region in MGE and pre-optic area at E13.5

• size of Nkx2-1-labeled region in MGE and pre-optic area at E10.5

• reduced size of Lhx8-labeled differentiating domain at E13.5

craniofacial

frontonasal prominence hypoplasia ( J:242687 )

• at E10.5 and E13.5

vision/eye

microphthalmia ( J:242687 )

• at E13.5

cellular

cellular phenotype ( J:242687 )

N • cell survival in telencephalon at E10.5 and E13.5

Genotype
MGI:5427352

cx60

• Allelic Composition: Smarca1^tm1.1Pick/Y; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * CD-1

nervous system

nervous system phenotype ( J:183998 )

♂N • no increase in the proportion of mitotic cells or fraction of intermediate/basal progenitor cells is detected at E15.5 unlike in mutant mice wild-type for Foxg1