Phenotypes Associated with This Genotype

Genotype
MGI:3513306

• Allelic Composition: Tcof1^tm1Mjd/Tcof1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1

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

Analysis of Tcof1^tm1Mjd/Tcof1⁺ embryos

mortality/aging

neonatal lethality, complete penetrance ( J:112900 )

• on a mixed C57BL/6 x DBA genetic background, heterozygotes die within 24 hrs of birth from respiratory arrest

• Background Sensitivity: on a congenic DBA genetic background, heterozygosity is compatible with postnatal life

craniofacial

abnormal craniofacial morphology ( J:112900 )

• heterozygotes exhibit severe midfacial anomalies characteristic of severe cases of Treacher Collins syndrome in humans

abnormal neurocranium morphology ( J:112900 )

abnormal temporal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic temporal bone

temporal bone hypoplasia ( J:112900 )

• at E17.5

abnormal viscerocranium morphology ( J:112900 )

abnormal frontal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic frontal bone

frontal bone hypoplasia ( J:112900 )

• at E15.5

mandible hypoplasia ( J:112900 )

• at E17.5

abnormal maxilla morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic maxilla

abnormal premaxilla morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic premaxilla

premaxilla hypoplasia ( J:112900 )

• at E15.5

short premaxilla ( J:112900 )

• at E17.5

maxilla hypoplasia ( J:112900 )

• at E15.5

short maxilla ( J:112900 )

• at E17.5

abnormal nasal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic nasal bone

nasal bone hypoplasia ( J:112900 )

• at E17.5

abnormal palatine bone morphology ( J:112900 )

• at E17.5, heterozygotes display dysmorphic palatine bones

palatine bone hypoplasia ( J:112900 )

• at E17.5

absent turbinates ( J:112900 )

• at E14.5, heterozygotes lack nasal conchae

domed cranium ( J:112900 )

• at E17.5, heterozygotes display a domed cranial vault

abnormal palatal shelf fusion at midline ( J:112900 )

• at E14.5, palatal shelves display absence of complete midline fusion

cleft palate ( J:112900 )

• at E17.5, heterozygotes display cleft palate

abnormal nasal cavity morphology ( J:112900 )

• neonatal heterozygotes display severe frontonasal dysplasia

• at E14.5, nasal passages are poorly formed

absent nasal septum ( J:112900 )

• at E14.5, heterozygotes lack a nasal septum

shortened head ( J:112900 )

• neonatal heterozygotes exhibit a shortened head in the anteroposterior direction

skeleton

abnormal neurocranium morphology ( J:112900 )

abnormal temporal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic temporal bone

temporal bone hypoplasia ( J:112900 )

• at E17.5

abnormal viscerocranium morphology ( J:112900 )

abnormal frontal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic frontal bone

frontal bone hypoplasia ( J:112900 )

• at E15.5

mandible hypoplasia ( J:112900 )

• at E17.5

abnormal maxilla morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic maxilla

abnormal premaxilla morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic premaxilla

premaxilla hypoplasia ( J:112900 )

• at E15.5

short premaxilla ( J:112900 )

• at E17.5

maxilla hypoplasia ( J:112900 )

• at E15.5

short maxilla ( J:112900 )

• at E17.5

abnormal nasal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic nasal bone

nasal bone hypoplasia ( J:112900 )

• at E17.5

abnormal palatine bone morphology ( J:112900 )

• at E17.5, heterozygotes display dysmorphic palatine bones

palatine bone hypoplasia ( J:112900 )

• at E17.5

absent turbinates ( J:112900 )

• at E14.5, heterozygotes lack nasal conchae

domed cranium ( J:112900 )

• at E17.5, heterozygotes display a domed cranial vault

respiratory system

abnormal nasal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic nasal bone

nasal bone hypoplasia ( J:112900 )

• at E17.5

absent turbinates ( J:112900 )

• at E14.5, heterozygotes lack nasal conchae

abnormal nasal cavity morphology ( J:112900 )

• neonatal heterozygotes display severe frontonasal dysplasia

• at E14.5, nasal passages are poorly formed

absent nasal septum ( J:112900 )

• at E14.5, heterozygotes lack a nasal septum

respiratory distress ( J:112900 )

• neonatal heterozygotes display gasping behavior

respiratory failure ( J:112900 )

• newborn heterozygotes exhibit respiratory arrest due to defects in the nasal, premaxilla, maxilla, and palatine elements

nervous system

increased embryonic neuroepithelium apoptosis ( J:112900 )

• at E8-E9.5, heterozygotes display a significantly high level of neuroepithelial-specific apoptosis, that is largely confined to the neural plate

abnormal neural plate morphology ( J:112900 )

• heterozygotes exhibit a significantly thinner neural plate during neural crest cell induction (E8.75)

decreased neural crest cell number ( J:112900 )

• NCC hypoplasia is due to defects in NCC formation and proliferation, is a direct consequence of neuroepithelial-specific apoptosis, and results in hypoplasia of the cranial sensory ganglia and skeletal elements

abnormal cranial ganglia morphology ( J:112900 )

• at E10.5, cranial sensory ganglia are formed in appropriate axial locations but appear significantly smaller and disorganized

decreased embryonic neuroepithelial cell proliferation ( J:112900 )

• in culture, E8.5-E9.0 heterozygotes show a significant reduction of cell proliferation in the neural plate and neural crest

• increased apoptosis and reduced cell proliferation is caused by deficient production of mature ribosomes in the neuroepithelium and neural crest

digestive/alimentary system

palatine bone hypoplasia ( J:112900 )

• at E17.5

abnormal palatal shelf fusion at midline ( J:112900 )

• at E14.5, palatal shelves display absence of complete midline fusion

cleft palate ( J:112900 )

• at E17.5, heterozygotes display cleft palate

growth/size/body

abnormal nasal bone morphology ( J:112900 )

• at E17.5, heterozygotes display a dysmorphic nasal bone

nasal bone hypoplasia ( J:112900 )

• at E17.5

palatine bone hypoplasia ( J:112900 )

• at E17.5

absent turbinates ( J:112900 )

• at E14.5, heterozygotes lack nasal conchae

abnormal palatal shelf fusion at midline ( J:112900 )

• at E14.5, palatal shelves display absence of complete midline fusion

cleft palate ( J:112900 )

• at E17.5, heterozygotes display cleft palate

abnormal nasal cavity morphology ( J:112900 )

• neonatal heterozygotes display severe frontonasal dysplasia

• at E14.5, nasal passages are poorly formed

absent nasal septum ( J:112900 )

• at E14.5, heterozygotes lack a nasal septum

shortened head ( J:112900 )

• neonatal heterozygotes exhibit a shortened head in the anteroposterior direction

microcephaly ( J:112900 )

• neonatal heterozygotes display a reduction in the size of the head

distended abdomen ( J:112900 )

• neonatal heterozygotes show abdominal distension

cellular

increased embryonic neuroepithelium apoptosis ( J:112900 )

• at E8-E9.5, heterozygotes display a significantly high level of neuroepithelial-specific apoptosis, that is largely confined to the neural plate

abnormal cranial neural crest cell migration ( J:112900 )

• at E9.5, fewer migrating NCCs from r2 and r4 populate the first branchial arch and second branchial arch, respectively

• at E10.5, heterozygotes show ~22% fewer migrating cranial NCCs in craniofacial mesenchyme relative to wild-type mice

decreased cranial neural crest cell proliferation ( J:112900 )

• NCC hypoplasia is due to defects in NCC formation and proliferation, is a direct consequence of neuroepithelial-specific apoptosis

embryo

abnormal cranial neural crest cell migration ( J:112900 )

• at E9.5, fewer migrating NCCs from r2 and r4 populate the first branchial arch and second branchial arch, respectively

• at E10.5, heterozygotes show ~22% fewer migrating cranial NCCs in craniofacial mesenchyme relative to wild-type mice

decreased cranial neural crest cell proliferation ( J:112900 )

• NCC hypoplasia is due to defects in NCC formation and proliferation, is a direct consequence of neuroepithelial-specific apoptosis

abnormal neural plate morphology ( J:112900 )

• heterozygotes exhibit a significantly thinner neural plate during neural crest cell induction (E8.75)

decreased neural crest cell number ( J:112900 )

• NCC hypoplasia is due to defects in NCC formation and proliferation, is a direct consequence of neuroepithelial-specific apoptosis, and results in hypoplasia of the cranial sensory ganglia and skeletal elements

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Treacher Collins syndrome		DOID:2908	OMIM:PS154500	J:112900