Analysis Tools
mortality/aging
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• homozygous mice die perinatally
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Allele Symbol Allele Name Allele ID |
Foxg1tm1(cre)Skm targeted mutation 1, Susan K McConnell MGI:1932522 |
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| Summary |
60 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygous mice die perinatally
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• volume of prosencephalon is reduced by 23%
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• 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
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• volume of striatum is reduced by 29.7%
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• 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
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• volume of hippocampus is reduced by 18.6%
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• 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
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• numbers of large and medium sized neurons are reduced in superficial layers of cortex
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• Background Sensitivity: thinning is observed only in C57BL/6 background, not in mixed C57BL/6 and CBA background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• cortical visual acuity is reduced at P30
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• decrease in spine density, but not spine length, in the basal dendrites of pyramidal cells (layer 2/3) in visual cortices
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Rett syndrome | DOID:1206 |
OMIM:312750 OMIM:613454 |
J:235875 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• cell survival and cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity
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| N |
• brain morphology at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5
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• reduction in size across A/P and D/V axes at E12.5
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• absent at E13.5 according to lack of Lhx8- and Nkx2-1-labeling of LGE region
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• absent at E13.5 according to lack of Lhx8- and Nkx2-1-labeling of MGE region
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• at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5
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• reduction in size across A/P and D/V axes at E12.5
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• at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity
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• according to TUNEL assay at E8.75
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• at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cochlear ducts show variability in length
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• less severely affected embryos display truncation of lateral canals
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• not discernible in most severely affected embryos at E13.5
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• not discernible in most severely affected embryos at E13.5
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• malformed in most severely affected embryos at E13.5
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• malformed in most severely affected embryos at E13.5
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• intact endolymphatic duct only is evident in dorsal region of inner ear
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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)
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• at E17.5, mutants appear edematous
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• at E17.5, mutants display severe malformations of craniofacial bone structures
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• at E17.5, mutants display fused basisphenoid and basioccipital bones
(J:109536)
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• zygomatic arch is missing
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• hyoid bone is hypoplastic
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• mandible is shorter than in wild-type
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• 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)
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• in conditional mutants, the masseter muscle is absent
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• in conditional mutants, pterygoid muscles are absent
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• observed at E17.5
(J:105980)
• at E17.5, mutants exhibit cleft palate
(J:109536)
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• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop
(J:109536)
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• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop
(J:109536)
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• at E10.5 or later
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• 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
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• at E17.5, mutants display a cystic endolymphatic duct
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• at E17.5, the otic capsule is hypoplastic
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• at E17.5, mutants show complete aplasia of inner ear sensory organs
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• at E17.5, mutants exhibit severe hypoplasia of the inner ear, developing only a cystic OV and endolymphatic duct
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• 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
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• 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)
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• at E10.5, the pharyngeal endoderm fails to invaginate toward the surface endoderm to form the tubotympanic recess
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• at E17.5, mutants lack tympanic rings
(J:109536)
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• pharynx in conditional null embryos is hypoplastic, lacking distal arches; the first pouch appears to be hypoplastic
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• at E17.5, mutants display severe malformations of craniofacial bone structures
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• at E17.5, mutants display fused basisphenoid and basioccipital bones
(J:109536)
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• zygomatic arch is missing
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• hyoid bone is hypoplastic
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• mandible is shorter than in wild-type
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• 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)
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• all null mutants have aortic arch defects
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• mutants have retroesophageal right subclavian artery
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• at E10.5 all conditional mutants display hypoplasia of the outflow tract
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• all conditional null mutants have a single outflow tract
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• in mutants the left ventricle communicates with the right through a large VSD
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• thyroid glands are smaller than wild-type and ectopically placed in conditional null embryos while conditional heterozygous embryos have ectopically placed thyroid glands
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• in conditional mutants, the masseter muscle is absent
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• in conditional mutants, pterygoid muscles are absent
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• observed at E17.5
(J:105980)
• at E17.5, mutants exhibit cleft palate
(J:109536)
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• 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
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• at E10.5, the first pharyngeal pouch fails to outgrow, preventing middle ear bone condensations
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• at E17.5, mutants appear edematous
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• in conditional mutants, the masseter muscle is absent
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• in conditional mutants, pterygoid muscles are absent
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• observed at E17.5
(J:105980)
• at E17.5, mutants exhibit cleft palate
(J:109536)
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• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop
(J:109536)
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| DiGeorge syndrome | DOID:11198 |
OMIM:188400 |
J:105980 , J:109536 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increases in inner hair cell number are more than in Dll1tm1Gos/Dll1tm2Gos Jag2tm1Grid/Jag2tm1Grid mice
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• decreases in inner hair cell number are slightly than in Dll1tm1Gos/Dll1tm2Gos Jag2tm1Grid/Jag2tm1Grid mice or Dll1tm1Gos Jag2tm1Grid homozygotes
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• increases in inner hair cell number are more than in Dll1tm1Gos/Dll1tm2Gos Jag2tm1Grid/Jag2tm1Grid mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decrease in the number of proliferating cells in the otic epithelium at E10.5
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• truncated or hypoplastic
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• decrease in the number of proliferating cells at E9.5 but not at E10.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die within 1 day of birth with no obvious milk in the stomach
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• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion
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• severe defects in cochlear structures
• severely hypoplastic
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• undulating appearance in the middle turn of the cochlea
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• 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
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• undercoiled with abnormal twisting at the apex
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• absent cristae
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• hypoplastic
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• severe defects in vestibular structures
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• hypoplastic
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• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion
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• 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
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• 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)
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• severe reduction in the number of neuroblasts in the otic epithelium and vestibulocochlear ganglion at E9.5, E10.5 and E11.5
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• at E12.5
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• medially displaced eyes at E12.5
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• die within 1 day of birth with no obvious milk in the stomach
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• reductions in cellular proliferation at E10.5 in both the otic epithelium and the vestibulocochlear ganglion
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• at E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe
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• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant mice die at birth due to defects in forebrain development
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• at birth, mutants exhibit lethal defects in forebrain development
• however, overall development of the inner ear and cochlea appeared normal
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• at E18.5, IHCs and OHCs appear to be in direct contact with each other in some cochlear sections
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• at E18.5, mutant mice show a significant reduction in the size and number of pillar cells (PCs) relative to control mice
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• 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
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• at E18.5, pillar cells are missing or underdeveloped
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe
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• apoptosis in the telencephalon is increased in a qualitatively similar manner to the Fgf8 conditional KOs, but is more severe
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• conditional mutants (males) die by E17
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• 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
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• 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)
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• there is a marked increase in cell death in postmitotic cell regions
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• 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
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• mutant neurites have few mitochondria vs wild-type
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• expression of complex I respiratory chain complex is abrogated in mutants
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• 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)
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• there is a marked increase in cell death in postmitotic cell regions
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• cortical thickness is reduced, mostly at the cortical plate (CP) and intermediate zone (IZ) and to lesser extent the subventricular zone (SVZ)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the apical/ventricular surface is disorganized
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• increasing incidence of exencephaly from E13.5 to E14.5
• exencephalic mass consists of greatly expanded neural progenitors
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• exencephalic mass consists of greatly expanded neural progenitors
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• Nkx2.1+ progenitor cells in the medial ganglionic eminence are mispecified
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• numbers of homozygotes starts to decline after E13.5
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• 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
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• 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
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• roof plate lacks invagination of dorsal telencephalon at E12.5
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• between E9.5-12.5, mutants do not exhibit enlargement of telencephalic vesicles in contrast to wild-type embryos
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• in E9.5-12.5 mutants, eye development is delayed compared to wild-type
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in cell death in the retina between P5 and P21 and cell death increases, especially in the ganglion cell layer, with age
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• 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
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• anterior segment is generally normal although pupillary ectopia is occasionally seen
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• the lens thickness increases during postnatal development as in wild-type eyes but is lower at P330 and P390
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• shorter inter-ocular distance
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• bilateral eye enlargement
• eyes are 30% and 40% longer at P60 and P180
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• 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
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• cell density in the ganglion cell layer is first decreased at P15
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• bipolar cells exhibit atrophic dendrites and their connections with the retinal ganglion cells appear thicker
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• reduction in the number of axons in the optic nerve at P150
• the optic nerve diameter is slightly increased at P150
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• peripapillary atrophy of the pigment epithelium consistent with a peripapillary staphyloma, a trait of myopic retinopathy
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• widespread pigment dispersion affects most of the retina
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• 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
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• significant reduction of the inner plexiform layer thickness from P7 onwards
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• 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
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• retinal thinning from P15 onwards
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• 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
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• scleral thickness at P90 and P180 is thinner by 33% and 50%, respectively
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• intraocular pressure is lower at P330 and P390 but normal at other times
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• increase in cell death in the retina between P5 and P21 and cell death increases, especially in the ganglion cell layer, with age
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• reduction of the proliferation index is seen at P3 and P5 in the eyes
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• bipolar cells exhibit atrophic dendrites
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• cell density in the ganglion cell layer is first decreased at P15
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• bipolar cells exhibit atrophic dendrites and their connections with the retinal ganglion cells appear thicker
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• reduction in the number of axons in the optic nerve at P150
• the optic nerve diameter is slightly increased at P150
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• peripapillary atrophy of the pigment epithelium consistent with a peripapillary staphyloma, a trait of myopic retinopathy
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• widespread pigment dispersion affects most of the retina
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| degenerative myopia | DOID:11829 | J:238249 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cleft lip and/or palate
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• cleft lip and/or palate
|
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• cleft lip and/or palate
|
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• cleft lip and/or palate
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• cleft lip and/or palate
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• reduced thalamocortical synaptic interactions
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all (13 of 13) mice exhibited truncation of anterior facial structures
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• 5 of 13 mice exhibited cleft lip and/or palate
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• 5 of 13 mice exhibited cleft lip and/or palate
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• all (13 of 13) mice showed incomplete medial nasal prominence approximation along the facial midline, resulting in a facial midline cleft
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• mice exhibited malformations of the telencephalon
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• only 1 of 13 mice exhibited exencephaly
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• all (13 of 13) mice exhibited truncation of anterior facial structures
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• 5 of 13 mice exhibited cleft lip and/or palate
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• 5 of 13 mice exhibited cleft lip and/or palate
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• all (13 of 13) mice showed incomplete medial nasal prominence approximation along the facial midline, resulting in a facial midline cleft
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• 5 of 13 mice exhibited cleft lip and/or palate
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| N |
• none of the 13 mice analyzed showed ocular hypertelorism
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• 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
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• cultured neurons can maintain oxygen consumption after camptothecin treatment if anchored Pdcd8 is expressed
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• 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
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• 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
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• cortex is thickened compared to Pdcd8 conditional embryos
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fewer cortical neurons expressing Satb2
• however, the number of Foxp1 and total neuron numbers are normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• collapse of the membranes of the vestibular compartments
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• cristae degeneration
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Absence of vascular defects in the brains of embryonic day 18 Igs1tm11(CAG-Bgeo,-Edn2)Nat/Igs1+ Foxg1tm1(cre)Skm/Foxg1+
|
• early postnatal lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• nearly two-thirds do not survive to adulthood
• born in approximately Mendelian ratios (21%)
|
|
• 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
|
|
• 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
|
|
• significantly smaller pituitary in size
|
|
• increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants
|
|
• disorganized olfactory sensory neurons
|
|
• 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
|
|
• 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
|
|
• 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
|
|
• 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
|
|
• significantly smaller pituitary in size
|
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants survive through E18.5
|
| N |
• at E15.5, inner ear structures not associated with sensory formation such as endolymphatic duct and sac, and crus are not affected
|
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no myelination in dorsal cortex while myelination in ventral cortex is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• inner ear develops normally
|
| N |
• spiral ganglion neuron neurite organization is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer mice survive to birth than expected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all die between E12.5 and E14.5
• only necrotic embryos are found at E14.5
|
|
• recessed jaws
|
|
• recessed snout
|
|
• severely deficient
|
| N |
• despite Cre-mediated deletion in the telencephalon, no defects in telencephalic patterning or development are detected
|
|
• recessed jaws
|
|
• recessed snout
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bilateral cleft lip in all mice
|
|
• bilateral cleft lip in all mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice seldom survive to adulthood
|
| N |
• stereocilia are apparently normal at 2 days of age
• stereocilia are still present at 21 days of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no obvious abnormalities in cochlea morphology is observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bilateral cleft lip
|
|
• in the nasal epithelial at E10.75
|
|
• bilateral cleft lip
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• abnormal maxillary palatal and palatine process
|
|
• the premaxillary process is absent
|
|
• bilateral cleft lip
|
|
• abnormal maxillary palatal and palatine process
|
|
• abnormal maxillary palatal and palatine process
|
|
• the premaxillary process is absent
|
|
• abnormal maxillary palatal and palatine process
|
|
• bilateral cleft lip
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bilateral cleft lip in all mice
|
|
• bilateral cleft lip in all mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at birth
|
|
• 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
|
|
• at E12.5
|
|
• at midgestation
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutant males die within 24 - 48 hours of birth, with only 1 male surviving to 24 days of age
|
|
|
• mutant males lack milk in their stomachs
|
|
|
• mutant males do not suckle well
|
|
|
• mutants are smaller at birth
|
|
|
• the dentate gyrus is replaced by a mass of disorganized cells
|
|
|
• reduced numbers of CA1 and CA3 pyramidal neurons are seen
|
|
|
• the subiculum and hippocampus are reduced in size
|
|
|
• 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 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at birth the apical hair cells show severe bundle misorientation
|
|
• at birth the apical hair cells show severe bundle misorientation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Thymic aplasia, nasal malformations, and eye, pharyngeal and ear defects in Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+ Foxg1tm1(cre)Skm/Foxg1+ mice and microcephaly, ocular and ear defects in Gt(ROSA)26Sortm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor+ Tg(Pax2-cre)1Akg/0 mice
|
• hypoplastic to varying degrees, but enlarged in two instances
|
|
• enlarged at E14.5
|
|
• enlarged at E14.5
|
|
• abnormal size and misguided projections
|
|
• abnormal size and misguided projections
|
|
• abnormal size and misguided projections
|
|
• abnormal size and misguided projections
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• 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
|
|
• 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
|
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die within 24 hrs after birth
|
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• died of respiratory failure within 30 min after birth, however decreased body size was not observed as in homozygous Top2b mutant mice
|
|
• lack the vigor of wild-type newborns, however show some body movements upon tactile stimulation
|
|
• collapsed lung alveoli in dead pups suggests respiratory failure
|
|
• ill-defined granule cell layer in the hippocampus
|
|
• ill-defined pyramidal cell layer in the hippocampus
|
|
• thinner cortex
|
|
• less developed olfactory bulb
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice fail to survive until adulthood
|
|
• mice are moderately dehydrated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• differentiating field of cortical GABAergic interneurons at E13.5 according to Shh and Lhx6 labeling
|
|
• reduced size of Dlx2-labeled region at E13.5
|
|
• reduction in size across A/P (-24%) and D/V (-16%) axes at E13.5
|
|
• reduced cell division at E13.5 according to mitotic marker p-HH3 immunoreactivity
|
|
• reduction in subset of dopaminergic olfactory interneuron progenitors in dorsal LGE at E13.5 according to Pax6 labeling
|
|
• 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
|
|
• at E10.5 and E13.5
|
|
• at E13.5
|
| N |
• cell survival in telencephalon at E10.5 and E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 07/02/2024 MGI 6.13 |
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