Mouse Genome Informatics
hm1
    Foxg1tm1(cre)Skm/Foxg1tm1(cre)Skm
129(Cg)-Foxg1tm1(cre)Skm/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygous mice die perinatally


Mouse Genome Informatics
ht2
    Foxg1tm1(cre)Skm/Foxg1+
129(Cg)-Foxg1tm1(cre)Skm/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities


Mouse Genome Informatics
ht3
    Foxg1tm1(cre)Skm/Foxg1+
B6.129P2-Foxg1tm1(cre)Skm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• volume of prosencephalon is reduced by 23%
• 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
• volume of striatum is reduced by 29.7%
• 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
• volume of hippocampus is reduced by 18.6%
• 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
• numbers of large and medium sized neurons are reduced in superficial layers of cortex
• Background Sensitivity: thinning is observed only in C57BL/6 background, not in mixed C57BL/6 and CBA background


Mouse Genome Informatics
ht4
    Foxg1tm1(cre)Skm/Foxg1+
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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


Mouse Genome Informatics
cn5
    Bmp4tm1Blh/Bmp4tm4Blh
Foxg1tm1(cre)Skm/Foxg1+

involves: 129 * Black Swiss * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• cochlear ducts show variability in length
• less severely affected embryos display truncation of lateral canals
• not discernible in most severely affected embryos at E13.5
• not discernible in most severely affected embryos at E13.5
• malformed in most severely affected embryos at E13.5; intact endolymphatic duct only is evident in dorsal region of inner ear
• malformed in most severely affected embryos at E13.5; intact endolymphatic duct only is evident in dorsal region of inner ear


Mouse Genome Informatics
cn6
    Chd7Gt(S20-7E1)Sor/Chd7tm1.1Dmm
Foxg1tm1(cre)Skm/Foxg1+

involves: 129 * C57BL/6 * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die within 1 day of birth with no obvious milk in the stomach

hearing/vestibular/ear
• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion
• severe defects in cochlear structures
• severely hypoplastic
• undercoiled with abnormal twisting at the apex
• severe defects in vestibular structures
• hypoplastic

nervous system
• severe reduction in the number of neuroblasts in the otic epithelium and vestibulocochlear ganglion at E9.5, E10.5 and E11.5
• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion
• about 1.5 fold smaller at E10.5-E12.5 compared to heterozygous and wild-type controls
• reduction in cellular proliferation at E10.5 in the vestibulocochlear ganglion

craniofacial
• at E12.5

vision/eye
• medially displaced eyes at E12.5

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

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


Mouse Genome Informatics
cn7
    Chd7tm1.1Dmm/Chd7+
Foxg1tm1(cre)Skm/Foxg1+

involves: 129 * C57BL/6 * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• decrease in the number of proliferating cells in the otic epithelium at E10.5
• truncated or hypoplastic

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


Mouse Genome Informatics
cn8
    Foxg1tm1(cre)Skm/Foxg1+
Notch1tm1Grid/Notch1tm2Rko

involves: 129 * C57BL/6J * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• increases in inner hair cell number are more than in Dll1tm1Gos/Dll1tm2Gos Jag2tm1Grid/Jag2tm1Grid mice
• decreases in inner hair cell number are slightly than in Dll1tm1Gos/Dll1tm2Gos Jag2tm1Grid/Jag2tm1Grid mice or Dll1tm1Gos Jag2tm1Grid homozygotes

nervous system
• increases in inner hair cell number are more than in Dll1tm1Gos/Dll1tm2Gos Jag2tm1Grid/Jag2tm1Grid mice


Mouse Genome Informatics
cn9
    Bsndtm1Tjj/Bsndtm1Tjj
Foxg1tm1(cre)Skm/Foxg1+

involves: 129/Sv * 129P2/OlaHsd * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice fail to survive until adulthood

homeostasis/metabolism
• mice are moderately dehydrated

hearing/vestibular/ear


Mouse Genome Informatics
cn10
    Foxg1tm1(cre)Skm/Foxg1+
Tbx1tm2.1Bem/Tbx1tm2.2Bem

involves: 129/Sv * C57BL/6 * SJL * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• at E17.5, mutants appear edematous

craniofacial
• at E17.5, mutants display severe malformations of craniofacial bone structures
• at E17.5, mutants display fused basisphenoid and basioccipital bones (J:109536)
• zygomatic arch is missing
• hyoid bone is hypoplastic
• mandible is shorter than in wild-type
• 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)
• observed at E17.5 (J:105980)
• at E17.5, mutants exhibit cleft palate (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
• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)
• at E10.5 or later
• 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
• at E17.5, mutants display a cystic endolymphatic duct
• at E17.5, the otic capsule is hypoplastic
• at E17.5, mutants show complete aplasia of inner ear sensory organs
• at E17.5, mutants exhibit severe hypoplasia of the inner ear, developing only a cystic OV and endolymphatic duct
• 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
• 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)
• at E17.5, mutants lack tympanic rings (J:109536)

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

skeleton
• at E17.5, mutants display severe malformations of craniofacial bone structures
• at E17.5, mutants display fused basisphenoid and basioccipital bones (J:109536)
• zygomatic arch is missing
• hyoid bone is hypoplastic
• mandible is shorter than in wild-type
• 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
• all null mutants have aortic arch defects
• mutants have retroesophageal right subclavian artery
• at E10.5 all conditional mutants display hypoplasia of the outflow tract
• all conditional null mutants have a single outflow tract
• in mutants the left ventricle communicates with the right through a large VSD

endocrine/exocrine glands
• 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

muscle
• in conditional mutants, the masseter muscle is absent
• in conditional mutants, pterygoid muscles are absent

hematopoietic system

digestive/alimentary system
• observed at E17.5 (J:105980)
• at E17.5, mutants exhibit cleft palate (J:109536)

nervous system
• 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

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

integument
• at E17.5, mutants appear edematous

Mouse Models of Human Disease
OMIM IDRef(s)
DiGeorge Syndrome; DGS 188400 J:105980 , J:109536


Mouse Genome Informatics
cn11
    Fgf8tm1.3Mrt/Fgf8tm1.4Mrt
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

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


Mouse Genome Informatics
cn12
    Fgf8tm1.1Mrt/Fgf8tm1.4Mrt
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe

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


Mouse Genome Informatics
cn13
    Foxg1tm1(cre)Skm/Foxg1+
Aifm1tm2Pngr/Y

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• conditional mutants (males) die by E17 (J:112874)

cellular
• mitochondria in cultured neurites are short and fragmented (J:112874)
• 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 (J:112874)
• cultured neurons transfected with a mitochondrially-anchored Pdcd8 show similar survival to wild-type neurons expressing GFP (J:112874)
• after camptothecin treatment, neurons show increased survival vs wild-type over the first 12 hours (~45% loss vs ~55% in wild-type) (J:112874)
• there is a marked increase in cell death in postmitotic cell regions (J:112874)
• membrane potential is hyperpolarized relative to wild-type cells (J:112874)
• membrane potential hyperpolarization is restored to normal by expression of anchored Pdcd8 (J:112874)
• ATP production and oxygen consumption in cultured mutant neurons is restored by mitochondrially anchored Pdcd8 (J:112874)
• mutant neurites have few mitochondria vs wild-type (J:112874)

homeostasis/metabolism
• expression of complex I respiratory chain complex is abrogated in mutants (J:112874)

nervous system
• cultured neurons transfected with a mitochondrially-anchored Pdcd8 show similar survival to wild-type neurons expressing GFP (J:112874)
• after camptothecin treatment, neurons show increased survival vs wild-type over the first 12 hours (~45% loss vs ~55% in wild-type) (J:112874)
• there is a marked increase in cell death in postmitotic cell regions (J:112874)
• cortical thickness is reduced, mostly at the cortical plate (CP) and intermediate zone (IZ) and to lesser extent the subventricular zone (SVZ) (J:112874)


Mouse Genome Informatics
cn14
    Cdc42tm1Yizh/Cdc42tm1Yizh
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• numbers of homozygotes starts to decline after E13.5

nervous system
• 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
• 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
• roof plate lacks invagination of dorsal telencephalon at E12.5
• between E9.5-12.5, mutants do not exhibit enlargement of telencephalic vesicles in contrast to wild-type embryos

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

embryogenesis
• 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


Mouse Genome Informatics
cn15
    Fgf8tm1.2Mrt/Fgf8tm1.3Mrt
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant mice die at birth due to defects in forebrain development

nervous system
• at birth, mutants exhibit lethal defects in forebrain development
• however, overall development of the inner ear and cochlea appeared normal

hearing/vestibular/ear
• at E18.5, IHCs and OHCs appear to be in direct contact with each other in some cochlear sections
• at E18.5, mutant mice show a significant reduction in the size and number of pillar cells (PCs) relative to control mice
• 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
• at E18.5, pillar cells are missing or underdeveloped
• 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
• 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


Mouse Genome Informatics
cn16
    Foxg1tm1(cre)Skm/Foxg1+
Gt(ROSA)26Sortm1(RARA*)Soc/Gt(ROSA)26Sortm1(RARA*)Soc

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• Nkx2.1+ progenitor cells in the medial ganglionic eminence are mispecified


Mouse Genome Informatics
cn17
    Celsr3tm1Agof/Celsr3tm2Agof
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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


Mouse Genome Informatics
cn18
    Foxg1tm1(cre)Skm/Foxg1+
Rhoatm1Yuyo/Rhoatm1Yuyo

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• exencephalic mass consists of greatly expanded neural progenitors
• the apical/ventricular surface is disorganized
• increasing incidence of exencephaly from E13.5 to E14.5
• exencephalic mass consists of greatly expanded neural progenitors

cellular
• exencephalic mass consists of greatly expanded neural progenitors


Mouse Genome Informatics
cn19
    Pbx1tm1Koss/Pbx1tm1Koss
Pbx3tm1Mlc/Pbx3+
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• cleft lip and/or palate
• cleft lip and/or palate

digestive/alimentary system
• cleft lip and/or palate


Mouse Genome Informatics
cn20
    Pbx1tm1Koss/Pbx1tm1Koss
Pbx2tm1Mlc/Pbx2+
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

craniofacial
• abnormal maxillary palatal and palatine process
• the premaxillary process is absent
• bilateral

respiratory system

digestive/alimentary system
• abnormal maxillary palatal and palatine process

skeleton
• abnormal maxillary palatal and palatine process
• the premaxillary process is absent


Mouse Genome Informatics
cn21
    Pbx1tm1Koss/Pbx1tm1Koss
Pbx2tm1Mlc/Pbx2tm1Mlc
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• bilateral

cellular
• in the nasal epithelial at E10.75


Mouse Genome Informatics
cn22
    Ntf3tm1Esm/Ntf3tm1Esm
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• 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
• reduced thalamocortical synaptic interactions
• 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


Mouse Genome Informatics
cn23
    Foxg1tm1(cre)Skm/Foxg1+
Jag1tm1Grid/Jag1tm2Grid

involves: 129P2/OlaHsd * 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants survive through E18.5

hearing/vestibular/ear
N
• at E15.5, inner ear structures not associated with sensory formation such as endolymphatic duct and sac, and crus are not affected (J:115783)
• formation of prosensory domain is disrupted by E18.5
• 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
• in apical turn of cochlea, there are only two rows instead of four rows of hair cells
• 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
• no outer hair cells or supporting Deiter's cells are present in apex of cochlea
• at E18.5, tunnel of Corti is not apparent
• semicircular canals are mostly absent, with only a small portion of lateral semicircular canal present at E15.5
• cristae and ampullae are missing or severely disrupted by E14.5 in homozygotes
• at E15.5, only a small portion of the anterior canal is present in homozygotes
• at E15.5, semicircular canals are largely absent
• structure is extremely small, with few differentiating hair cells; severe disruption of differentiation of utricular macula is observed
• observed at E13.5
• 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
• 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
• in apical turn of cochlea, there are only two rows instead of four rows of hair cells
• 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
• no outer hair cells or supporting Deiter's cells are present in apex of cochlea


Mouse Genome Informatics
cn24
    Apaf1Gt(IRESBetageo)XIX18Pgr/Apaf1Gt(IRESBetageo)XIX18Pgr
Foxg1tm1(cre)Skm/Foxg1+
Aifm1tm2Pngr/Y

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• neurons show increased survival vs wild-type after camptothecin treatment (J:112874)
• neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment (J:112874)
• expression of anchored Pdcd8 does not provide further protection from death to neurons (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 (J:112874)
• cultured neurons can maintain oxygen consumption after camptothecin treatment if anchored Pdcd8 is expressed (J:112874)

nervous system
• neurons show increased survival vs wild-type after camptothecin treatment (J:112874)
• neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment (J:112874)
• expression of anchored Pdcd8 does not provide further protection from death to neurons (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 (J:112874)
• cortex is thickened compared to Pdcd8 conditional embryos (J:112874)


Mouse Genome Informatics
cn25
    Gt(ROSA)26Sortm1Red/Gt(ROSA)26Sor+
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• fewer cortical neurons expressing Satb2
• however, the number of Foxp1 and total neuron numbers are normal


Mouse Genome Informatics
cn26
    Slc12a2tm1.1Jheb/Slc12a2tm1.1Jheb
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological

hearing/vestibular/ear
• collapse of the membranes of the vestibular compartments
• cristae degeneration


Mouse Genome Informatics
cn27
    Foxg1tm1(cre)Skm/Foxg1+
Igs1tm11(CAG-Bgeo,-Edn2)Nat/Igs1+

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• early postnatal lethality

craniofacial

vision/eye

digestive/alimentary system


Mouse Genome Informatics
cn28
    Notch2tm3Grid/Notch2tm3Grid
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• nearly two-thirds do not survive to adulthood
• born in approximately Mendelian ratios (21%)

growth/size
• 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
• increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants
• significantly smaller pituitary in size
• disorganized olfactory sensory neurons
• lower Glutathione S-transferase activity in mutant olfactory epithelia
• 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
• 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

taste/olfaction
• 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 TUNEL-positive cells in the apical layer of the olfactory epithelium (0.3 cells/mm vs. 0/mm)
• 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
• increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants

endocrine/exocrine glands
• significantly smaller pituitary in size

respiratory system
• 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
• 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


Mouse Genome Informatics
cn29
    Foxg1tm1(cre)Skm/Foxg1+
Olig2tm1Qrlu/Olig2tm1Qrlu

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• no myelination in dorsal cortex while myelination in ventral cortex is normal


Mouse Genome Informatics
cn30
    Lmo4tm1Gan/Lmo4tm2.1Gan
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• at E15.5, mice exhibit vestibular defects observed in Lmo4tm1Gan homozygotes
• at E15.5, mice lack anterior and posterior ampullae unlike in wild-type mice


Mouse Genome Informatics
cn31
    Bmp4tm3Blh/Bmp4tm3Blh
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all die between E12.5 and E14.5
• only necrotic embryos are found at E14.5

craniofacial
• recessed jaws
• recessed snout

vision/eye
• severely deficient

nervous system
N
• despite Cre-mediated deletion in the telencephalon, no defects in telencephalic patterning or development are detected (J:83123)

skeleton
• recessed jaws


Mouse Genome Informatics
cn32
    Bmp4tm3Blh/Bmp4+
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer mice survive to birth than expected


Mouse Genome Informatics
cn33
    Pbx1tm1Mlc/Pbx1+
Wnt9btm1Amc/Wnt9btm1Amc
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S6/SvEvTac * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• bilateral in all mice

digestive/alimentary system


Mouse Genome Informatics
cn34
    Actbtm1.1Erv/Actbtm1.1Erv
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice seldom survive to adulthood

hearing/vestibular/ear
N
• stereocilia are apparently normal at 2 days of age (J:167543)
• stereocilia are still present at 21 days of age (J:167543)


Mouse Genome Informatics
cn35
    Lmo4tm2.1Gan/Lmo4tm2.1Gan
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• at E15.5, mice exhibit vestibular defects observed in Lmo4tm1Gan homozygotes
• at E15.5, mice lack anterior and posterior ampullae unlike in wild-type mice


Mouse Genome Informatics
cn36
    Bmp2tm1Brd/Bmp2tm1.1Mis
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
N
• no obvious abnormalities in cochlea morphology is observed (J:156945)


Mouse Genome Informatics
cn37
    Wnt9btm1Amc/Wnt9btm1Amc
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• bilateral in all mice

digestive/alimentary system


Mouse Genome Informatics
cn38
    Foxg1tm1(cre)Skm/Foxg1+
Sp8tm2.1Aman/Sp8tm2.1Aman

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die at birth

nervous system
• 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
• 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
• 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
• 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
• 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+)
• mice exhibit dysgenesis of the olfactory bulb and septum, including an almost complete absence of the midline, compared with wild-type mice
• mild rostral
• the lateral ventricles are fused because of the complete disgenesis of the midline unlike in wild-type mice
• 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
• 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

craniofacial

cellular
• 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
• 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


Mouse Genome Informatics
cn39
    Atrxtm1Rjg/Y
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant males die within 24 - 48 hours of birth, with only 1 male surviving to 24 days of age (J:95953)

behavior/neurological
• mutant males lack milk in their stomachs (J:95953)
• mutant males do not suckle well (J:95953)

growth/size
• mutants are smaller at birth (J:95953)

nervous system
• the dentate gyrus is replaced by a mass of disorganized cells (J:95953)
• reduced numbers of CA1 and CA3 pyramidal neurons are seen (J:95953)
• the subiculum and hippocampus are reduced in size (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 (J:95953)
• cell numbers in the cortical plate are reduced by 20-30% (J:95953)
• cell loss is not seen at E13.5 but is significant at E15.5 (J:95953)


Mouse Genome Informatics
cn40
    Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

hearing/vestibular/ear
• hypoplastic to varying degrees, but enlarged in two instances
• enlarged at E14.5

nervous system
• abnormal size and misguided projections
• abnormal size and misguided projections
• abnormal size and misguided projections
• abnormal size and misguided projections

respiratory system

vision/eye

hematopoietic system
• thymic aplasia

craniofacial

taste/olfaction

immune system
• thymic aplasia


Mouse Genome Informatics
cn41
    Dll1tm1Mjo/Dll1tm1Mjo
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• 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
• 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
• 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
• 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
• the utricular macula is severely reduced or lost
• the saccular macula is severely reduced or lost

nervous system
• 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
• 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
• 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


Mouse Genome Informatics
cn42
    Fgfr1tm1Upir/Fgfr1tm1.1Upir
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die within 24 hrs after birth

hearing/vestibular/ear
• 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
• 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
• 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
• 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
• at P0, mutants show a 85% reduction in the total number of differentiating HCs relative to wild-type mice
• at birth, only very low numbers of OHCs are formed, and these are located in lower cochlear half
• at birth, the small sensory patches found in the upper cochlear half frequently show doublet IHCs instead of a single continuous IHC row
• at birth, the small sensory patches found in the upper cochlear half frequently show an accumulation of disorientated IHCs at the edges
• at birth, the sensory patches found in the upper cochlear half frequently show no signs of differentiation of supporting cells

nervous system
• 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
• at P0, mutants show a 85% reduction in the total number of differentiating HCs relative to wild-type mice
• at birth, only very low numbers of OHCs are formed, and these are located in lower cochlear half
• at birth, the small sensory patches found in the upper cochlear half frequently show doublet IHCs instead of a single continuous IHC row
• at birth, the small sensory patches found in the upper cochlear half frequently show an accumulation of disorientated IHCs at the edges


Mouse Genome Informatics
cn43
    Fgfr1tm1Upir/Fgfr1tm1Upir
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• phenotype is stated to be comparable to that of mice that are compound heterozygous for Fgfr1tm1.1Upir and Fgfr1tm1Upir and also heterozygous for Foxg1tm1(cre)Skm; however, no data are presented in J:78879

hearing/vestibular/ear


Mouse Genome Informatics
cn44
    Six3tm3Gco/Six3tm3Gco
Foxg1tm1(cre)Skm/Foxg1+

involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• many display a phenotype typical of holoprosencephaly
• anterior diencephalon is normal

Mouse Models of Human Disease
OMIM IDRef(s)
Holoprosencephaly 2; HPE2 157170 J:140315


Mouse Genome Informatics
cn45
    Foxg1tm1(cre)Skm/Foxg1+
Top2btm2Jcw/Top2btm2.1Jcw

involves: 129S4/SvJae * 129S6/SvEvTac * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• died of respiratory failure within 30 min after birth, however decreased body size was not observed as in homozygous Top2b mutant mice

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

respiratory system
• collapsed lung alveoli in dead pups suggests respiratory failure

nervous system
• ill-defined granule cell layer in the hippocampus
• ill-defined pyramidal cell layer in the hippocampus
• less developed olfactory bulb


Mouse Genome Informatics
cn46
    Foxg1tm1(cre)Skm/Foxg1+
Jag1tm1Jlew/Jag1tm1Jlew

involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• at E17.5, the middle part of the cochlea has two disorganized rows of hair cells instead of the normal stereotyped pattern of 3 rows of outer hair cells and 1 row of inner hair cells: towards base of the cochlea, the number of hair cells is severely reduced and instead of a continuous band of two rows, the rows are broken up and irregular islands of hair cells are present
• in mutants, the number of hair cells per 100 microns of cochlea length is reduced to 25.8 as compared to 63.5 in wild-type controls
• in conditional Jag1 knockouts, outer hair cells are missing completely
• number of inner hair cells is almost doubled from 15.3 per 100 microns cochlea length to 25.8
• epithelium where the horizontal crista and utricular macula would be lacks hair cells
• in Jag1 mutants, all three semicircular canals are truncated
• epithelium where the utricular macula would be is thickened

nervous system
• at E17.5, the middle part of the cochlea has two disorganized rows of hair cells instead of the normal stereotyped pattern of 3 rows of outer hair cells and 1 row of inner hair cells: towards base of the cochlea, the number of hair cells is severely reduced and instead of a continuous band of two rows, the rows are broken up and irregular islands of hair cells are present
• in mutants, the number of hair cells per 100 microns of cochlea length is reduced to 25.8 as compared to 63.5 in wild-type controls
• in conditional Jag1 knockouts, outer hair cells are missing completely
• number of inner hair cells is almost doubled from 15.3 per 100 microns cochlea length to 25.8
• epithelium where the horizontal crista and utricular macula would be lacks hair cells


Mouse Genome Informatics
cx47
    Foxg1tm1(cre)Skm/Foxg1+
Smarca1tm1.1Pick/Y

involves: 129P2/OlaHsd * 129S4/SvJae * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
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 (J:183998)