Phenotypes associated with this allele

• Allele Symbol: Tcof1^tm1Mjd
• Allele Name: targeted mutation 1, Michael J Dixon
• Allele ID: MGI:2386185
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Tcof1^tm1Mjd/Tcof1^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c	MGI:6280679
ht2	Tcof1^tm1Mjd/Tcof1^+	involves: 129S1/Sv * 129X1/SvJ * C3H/HeN	MGI:6280676
ht3	Tcof1^tm1Mjd/Tcof1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3029251
ht4	Tcof1^tm1Mjd/Tcof1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1	MGI:3513306
ht5	Tcof1^tm1Mjd/Tcof1^+	involves: 129S1/Sv * 129X1/SvJ * CBA/Ca	MGI:6280674
ht6	Tcof1^tm1Mjd/Tcof1^+	involves: 129S1/Sv * 129X1/SvJ * DBA/1	MGI:6280678

Genotype
MGI:6280679

ht1

• Allelic Composition: Tcof1^tm1Mjd/Tcof1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c

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

mortality/aging

mortality/aging ( J:89223 )

N • Background Sensitivity: non-exencephalic mice (71 of 76) are viable with a normal lifespan

nervous system

nervous system phenotype ( J:89223 )

N • Background Sensitivity: no abnormalities are seen in the cranial or dorsal root ganglia unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

exencephaly ( J:89223 )

• in 5 of 76 mice at E9 or older

• Background Sensitivity: decreased incidence compared to mice on a mixed background containing C57BL/6, C3H/HeN, or CBA/Ca

reproductive system

reproductive system phenotype ( J:89223 )

N • non-exencephalic mice (71 of 76) are fertile

behavior/neurological

behavior/neurological phenotype ( J:89223 )

N • Background Sensitivity: flexion of the spine or abnormal posture is not seen unlike in mice on a mixed background containing C57BL/6, CBA/Ca, or C3H/HeN

embryo

embryo phenotype ( J:89223 )

N • Background Sensitivity: no abnormalities are seen in the neural crest migration unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

limbs/digits/tail

limbs/digits/tail phenotype ( J:89223 )

N • Background Sensitivity: no digit abnormalities are seen unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

skeleton

skeleton phenotype ( J:89223 )

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6 or CBA/Ca hypoplasia of the mandible/maxilla and fusions of the cervical or thoracic vertebrae are not seen

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6, CBA/Ca, or DBA/1 rib fusions are not seen

N • Background Sensitivity: ossification delay of the long bones is not seen in mice on a mixed background containing C57BL/6, C3H/HeN, DBA/1 or BALB/c unlike mice on a mixed background containing CBA/Ca

vision/eye

vision/eye phenotype ( J:89223 )

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6 or CBA/Ca anophthalmia or microphthalmia are not seen

Genotype
MGI:6280676

ht2

• Allelic Composition: Tcof1^tm1Mjd/Tcof1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeN

nervous system

nervous system phenotype ( J:89223 )

N • Background Sensitivity: no abnormalities are seen in the cranial or dorsal root ganglia unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

exencephaly ( J:89223 )

• in 26 of 29 mice at E9 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1 or BALB/c

behavior/neurological

abnormal posture ( J:89223 )

• flexion of the spine or abnormal posture in 1 of 7 mice

vision/eye

small orbits ( J:89223 )

• exopthalmia or small orbits in all embryos

exophthalmos ( J:89223 )

• exopthalmia or small orbits in all embryos

embryo

embryo phenotype ( J:89223 )

N • Background Sensitivity: no abnormalities are seen in the neural crest migration unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

craniofacial

craniofacial phenotype ( J:89223 )

N • Background Sensitivity: no nasal complex abnormalities are seen unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

small orbits ( J:89223 )

• exopthalmia or small orbits in all embryos

growth/size/body

growth/size/body region phenotype ( J:89223 )

N • Background Sensitivity: do not display developmental display unlike mice on a mixed background containing C57BL/6 or CBA/Ca

limbs/digits/tail

limbs/digits/tail phenotype ( J:89223 )

N • Background Sensitivity: no digit abnormalities are seen unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

skeleton

skeleton phenotype ( J:89223 )

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6 or CBA/Ca hypoplasia of the mandible/maxilla and fusions of the cervical or thoracic vertebrae are not seen

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6, CBA/Ca, or DBA/1 rib fusions are not seen

N • Background Sensitivity: ossification delay of the long bones is not seen in mice on a mixed background containing C57BL/6, C3H/HeN, DBA/1 or BALB/c unlike mice on a mixed background containing CBA/Ca

small orbits ( J:89223 )

• exopthalmia or small orbits in all embryos

Genotype
MGI:3029251

ht3

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

mortality/aging

neonatal lethality, complete penetrance ( J:62928 )

• newborn heterozygotes are exencephalic, fail to establish an airway, and die shortly after birth

craniofacial

abnormal craniofacial morphology ( J:62928 )

• as early as E8, heterozygotes exhibit major craniofacial defects, not attributable solely to a developmental delay

abnormal craniofacial bone morphology ( J:62928 )

abnormal cranium morphology ( J:62928 )

• heterozygous skulls are grossly malformed

abnormal neurocranium morphology ( J:62928 )

• with the exception of the supraoccipital, the bones of the skull vault are absent

absent frontal bone ( J:62928 )

absent interparietal bone ( J:62928 )

absent parietal bone ( J:62928 )

abnormal zygomatic arch morphology ( J:62928 )

• the zygomatic arch is hypoplastic and misshapen

zygomatic arch hypoplasia ( J:62928 )

small mandible ( J:62928 )

• at E14.5 and E18, the mandibular component of the first arch is smaller

short mandible ( J:62928 )

• at E14.5 and E18, the mandibular component of the first arch is shorter

retrognathia ( J:62928 )

• at E12.5, heterozygotes show severe retrognathia of the middle third of the face

facial bone hypoplasia ( J:89223 )

• hypoplasia of the mandible/maxilla in all mice at E9 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

mandible hypoplasia ( J:62928 )

acrania ( J:62928 )

abnormal middle ear ossicle morphology ( J:62928 )

• the middle ear ossicles are hypoplastic and misshapen

middle ear ossicle hypoplasia ( J:62928 )

abnormal craniofacial development ( J:62928 )

frontonasal prominence hypoplasia ( J:62928 )

• at E9.5, heterozygous frontonasal processes are markedly hypoplastic

abnormal lateral nasal prominence morphology ( J:62928 )

• by E10.5, heterozygotes fail to develop either medial or lateral nasal processes

abnormal maxillary prominence morphology ( J:62928 )

• at E14.5 and E18, the maxillary component of the first arch is less distinct and displaced rostrally, and is hypoplastic

abnormal medial nasal prominence morphology ( J:62928 )

• by E10.5, heterozygotes fail to develop either medial or lateral nasal processes

abnormal nasal capsule morphology ( J:62928 )

• the nasal capsule is extremely dysmorphic with a midline cartilaginous protrusion

absent nasal pit ( J:62928 )

• at E12.5, heterozygotes fail to develop nasal pits

failure of palatal shelf elevation ( J:62928 )

• at E14.5, while the secondary palate of wild-type mice have elevated and fused, heterozygous palatal shelves appear severely disorganized and displaced

• however, incisor and molar tooth germs appear to develop normally

first pharyngeal arch hypoplasia ( J:62928 )

• heterozygotes display an underdeveloped first pharyngeal arch resulting in the formation of a rudimentary upper lip

abnormal upper lip morphology ( J:62928 )

• at E12.5, heterozygotes display only a rudimentary upper lip

abnormal nasal septum morphology ( J:89223 )

• midline nasal spear present in place of the septum in 4 of 4 embryos

abnormal outer ear morphology ( J:62928 )

lowered ear position ( J:62928 )

cup-shaped ears ( J:62928 )

respiratory system

abnormal nasal capsule morphology ( J:62928 )

• the nasal capsule is extremely dysmorphic with a midline cartilaginous protrusion

absent nasal pit ( J:62928 )

• at E12.5, heterozygotes fail to develop nasal pits

abnormal nasal septum morphology ( J:89223 )

• midline nasal spear present in place of the septum in 4 of 4 embryos

respiratory failure ( J:62928 )

• newborn heterozygotes fail to establish an airway, due to absence of nasal passages

skeleton

skeleton phenotype ( J:89223 )

N • Background Sensitivity: ossification delay of the long bones is not seen in mice on a mixed background containing C57BL/6, C3H/HeN, DBA/1 or BALB/c unlike mice on a mixed background containing CBA/Ca

abnormal craniofacial bone morphology ( J:62928 )

abnormal cranium morphology ( J:62928 )

• heterozygous skulls are grossly malformed

abnormal neurocranium morphology ( J:62928 )

• with the exception of the supraoccipital, the bones of the skull vault are absent

absent frontal bone ( J:62928 )

absent interparietal bone ( J:62928 )

absent parietal bone ( J:62928 )

abnormal zygomatic arch morphology ( J:62928 )

• the zygomatic arch is hypoplastic and misshapen

zygomatic arch hypoplasia ( J:62928 )

small mandible ( J:62928 )

• at E14.5 and E18, the mandibular component of the first arch is smaller

short mandible ( J:62928 )

• at E14.5 and E18, the mandibular component of the first arch is shorter

retrognathia ( J:62928 )

• at E12.5, heterozygotes show severe retrognathia of the middle third of the face

facial bone hypoplasia ( J:89223 )

• hypoplasia of the mandible/maxilla in all mice at E9 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

mandible hypoplasia ( J:62928 )

acrania ( J:62928 )

abnormal middle ear ossicle morphology ( J:62928 )

• the middle ear ossicles are hypoplastic and misshapen

middle ear ossicle hypoplasia ( J:62928 )

abnormal nasal capsule morphology ( J:62928 )

• the nasal capsule is extremely dysmorphic with a midline cartilaginous protrusion

rib fusion ( J:89223 )

• in 3 of 14 mice

vertebral fusion ( J:89223 )

• fusions of the cervical or thoracic vertebrae in 4 of 14 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

vision/eye

absent optic vesicle ( J:62928 )

• at E8.5, heterozygotes display absence of the optic evagination

anophthalmia ( J:62928 , J:89223 )

• by E14.5, heterozygotes exhibit anophthalmia (J:62928)

• in all embryos (J:89223)

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1 or BALB/c (J:89223)

nervous system

increased neural tube apoptosis ( J:62928 )

• at E8.5, elevated levels of cell death, particularly in the cephalic neural folds and neural tube

• level of apoptosis remains high throughout E9.0 to E9.5, particularly in the post-fusion neural tube

delayed neural tube closure ( J:62928 )

• at E9.0, most heterozygotes display a delay in the closure of the rostral neuropore resulting in exencephaly

open neural tube ( J:62928 )

• at E10.5, only a few heterozygotes succeed in closing their rostral neuropore but still display brain hypoplasia

abnormal midbrain development ( J:62928 )

• at E10.5, heterozygotes show a severely compromised midbrain development

abnormal forebrain morphology ( J:62928 )

• at E12.5, heterozygotes display a severely disorganized forebrain

abnormal Rathke's pouch development ( J:62928 )

• at E10.5, the entrance to Rathke's pouch is visible but smaller

abnormal forebrain development ( J:62928 )

• at E9.5, heterozygotes show no evidence of division of the forebrain into telencephalic or optic vesicles

exencephaly ( J:62928 , J:89223 )

• at E10.5, most heterozygotes exhibit exencephaly with neuroepithelium protruding through the open rostral neuropore (J:62928)

• in all mice at E9 or older (J:89223)

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1 or BALB/c (J:89223)

abnormal cranial ganglia morphology ( J:62928 , J:89223 )

• at E10.5, the neural crest cell-derived cranial ganglia are severely hypoplastic (J:62928)

• abnormal or hypoplastic in 11 of 11 mice (J:89223)

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c (J:89223)

small trigeminal ganglion ( J:62928 )

absent glossopharyngeal nerve ( J:62928 )

• at E10.5, the glossopharyngeal ganglia/nerves are absent

abnormal trigeminal nerve morphology ( J:62928 )

• at E10.5, the ophthalmic branch of the trigeminal nerve is absent

abnormal dorsal root ganglion morphology ( J:89223 )

• abnormal or hypoplastic in 11 of 11 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

disorganized dorsal root ganglion ( J:62928 )

• at E10.5, the dorsal root ganglia are underdeveloped and severely disorganized

embryo

abnormal neural crest cell migration ( J:89223 )

• in 11 of 11 mice

• Background Sensitivity: not seen in mice on a mixed background containing C3H/HeN, DBA/1 or BALB/c

first pharyngeal arch hypoplasia ( J:62928 )

• heterozygotes display an underdeveloped first pharyngeal arch resulting in the formation of a rudimentary upper lip

delayed embryo turning ( J:62928 )

• at E9.0, heterozygotes exhibit delayed axial turning relative to wild-type counterparts

embryonic growth retardation ( J:62928 )

• at >E8, heterozygotes display a generalized developmental delay of ~0.5-1 day that persists throughout development

abnormal neural fold formation ( J:62928 )

• at E8.5, heterozygotes display smaller, rounded neural folds

delayed neural tube closure ( J:62928 )

• at E9.0, most heterozygotes display a delay in the closure of the rostral neuropore resulting in exencephaly

open neural tube ( J:62928 )

• at E10.5, only a few heterozygotes succeed in closing their rostral neuropore but still display brain hypoplasia

growth/size/body

abnormal nasal capsule morphology ( J:62928 )

• the nasal capsule is extremely dysmorphic with a midline cartilaginous protrusion

failure of palatal shelf elevation ( J:62928 )

• at E14.5, while the secondary palate of wild-type mice have elevated and fused, heterozygous palatal shelves appear severely disorganized and displaced

• however, incisor and molar tooth germs appear to develop normally

abnormal upper lip morphology ( J:62928 )

• at E12.5, heterozygotes display only a rudimentary upper lip

abnormal nasal septum morphology ( J:89223 )

• midline nasal spear present in place of the septum in 4 of 4 embryos

abnormal outer ear morphology ( J:62928 )

lowered ear position ( J:62928 )

cup-shaped ears ( J:62928 )

prenatal growth retardation ( J:89223 )

• developmental delay in all mice at E8 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

embryonic growth retardation ( J:62928 )

• at >E8, heterozygotes display a generalized developmental delay of ~0.5-1 day that persists throughout development

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:62928 )

• the middle ear ossicles are hypoplastic and misshapen

middle ear ossicle hypoplasia ( J:62928 )

abnormal outer ear morphology ( J:62928 )

lowered ear position ( J:62928 )

cup-shaped ears ( J:62928 )

small otic vesicle ( J:62928 )

• at E12.5, heterozygotes display smaller otocysts

abnormal tympanic ring morphology ( J:62928 )

• the tympanic ring is misshapen and misplaced

tympanic ring hypoplasia ( J:62928 )

• the tympanic ring is hypoplastic

digestive/alimentary system

failure of palatal shelf elevation ( J:62928 )

• at E14.5, while the secondary palate of wild-type mice have elevated and fused, heterozygous palatal shelves appear severely disorganized and displaced

• however, incisor and molar tooth germs appear to develop normally

endocrine/exocrine glands

abnormal Rathke's pouch development ( J:62928 )

• at E10.5, the entrance to Rathke's pouch is visible but smaller

behavior/neurological

abnormal posture ( J:89223 )

• flexion of the spine or abnormal posture in 3 of 14 mice

cellular

increased neural tube apoptosis ( J:62928 )

• at E8.5, elevated levels of cell death, particularly in the cephalic neural folds and neural tube

• level of apoptosis remains high throughout E9.0 to E9.5, particularly in the post-fusion neural tube

abnormal neural crest cell migration ( J:89223 )

• in 11 of 11 mice

• Background Sensitivity: not seen in mice on a mixed background containing C3H/HeN, DBA/1 or BALB/c

limbs/digits/tail

abnormal digit morphology ( J:89223 )

• seen in 7 of 42 embryos at age E13 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Treacher Collins syndrome		DOID:2908	OMIM:PS154500	J:62928

Genotype
MGI:3513306

ht4

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

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

Genotype
MGI:6280674

ht5

• Allelic Composition: Tcof1^tm1Mjd/Tcof1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CBA/Ca

nervous system

exencephaly ( J:89223 )

• in 31 of 33 mice at E9 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1 or BALB/c

abnormal cranial ganglia morphology ( J:89223 )

• abnormal or hypoplastic in 6 of 6 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

abnormal dorsal root ganglion morphology ( J:89223 )

• abnormal or hypoplastic in 6 of 6 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

behavior/neurological

abnormal posture ( J:89223 )

• in 4 of 4 mice

vision/eye

abnormal eye morphology ( J:89223 )

• unilateral anophthalmia or microphthalmia in all embryos

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

embryo

abnormal neural crest cell migration ( J:89223 )

• in 6 of 6 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

craniofacial

facial bone hypoplasia ( J:89223 )

• hypoplasia of the mandible/maxilla in all mice at E9 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

abnormal nasal septum morphology ( J:89223 )

• midline nasal spear present in place of the septum in 4 of 4 embryos

• increased incidence compared to mice on a mixed background containing C3H/HeN or BALB/c

growth/size/body

abnormal nasal septum morphology ( J:89223 )

• midline nasal spear present in place of the septum in 4 of 4 embryos

• increased incidence compared to mice on a mixed background containing C3H/HeN or BALB/c

prenatal growth retardation ( J:89223 )

• developmental delay in all mice at E8 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN or BALB/c

limbs/digits/tail

abnormal digit morphology ( J:89223 )

• seen in 9 of 15 embryos at age E13 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

skeleton

facial bone hypoplasia ( J:89223 )

• hypoplasia of the mandible/maxilla in all mice at E9 or older

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

rib fusion ( J:89223 )

• in 4 of 4 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing C3H/HeN or BALB/c

vertebral fusion ( J:89223 )

• fusions of the cervical or thoracic vertebrae in 4 of 4 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing C3H/HeN or BALB/c

delayed endochondral bone ossification ( J:89223 )

• delayed ossification of the long bones in 7 of 7 mice

• Background Sensitivity: ossification delay is not seen in mice on a mixed background containing C57BL/6, C3H/HeN, DBA/1 or BALB/c

cellular

abnormal neural crest cell migration ( J:89223 )

• in 6 of 6 mice

• Background Sensitivity: increased incidence compared to mice on a mixed background containing DBA/1, C3H/HeN, or BALB/c

respiratory system

abnormal nasal septum morphology ( J:89223 )

• midline nasal spear present in place of the septum in 4 of 4 embryos

• increased incidence compared to mice on a mixed background containing C3H/HeN or BALB/c

Genotype
MGI:6280678

ht6

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

mortality/aging

mortality/aging ( J:89223 )

N • non-exencephalic mice (71 of 76) are viable with a normal lifespan

nervous system

nervous system phenotype ( J:89223 )

N • Background Sensitivity: no abnormalities are seen in the cranial or dorsal root ganglia unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

exencephaly ( J:89223 )

• in 5 of 76 mice at E9 or older

• Background Sensitivity: decreased incidence compared to mice on a mixed background containing C57BL/6, C3H/HeN, or CBA/Ca

reproductive system

reproductive system phenotype ( J:89223 )

N • non-exencephalic mice (71 of 76) are fertile

behavior/neurological

behavior/neurological phenotype ( J:89223 )

N • Background Sensitivity: flexion of the spine or abnormal posture is not seen unlike in mice on a mixed background containing C57BL/6, CBA/Ca, or C3H/HeN

embryo

embryo phenotype ( J:89223 )

N • Background Sensitivity: no abnormalities are seen in the neural crest migration unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

limbs/digits/tail

limbs/digits/tail phenotype ( J:89223 )

N • Background Sensitivity: no digit abnormalities are seen unlike in mice on a mixed background containing C57BL/6 or CBA/Ca

skeleton

skeleton phenotype ( J:89223 )

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6 or CBA/Ca hypoplasia of the mandible/maxilla and fusions of the cervical or thoracic vertebrae are not seen

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6, CBA/Ca, or DBA/1 rib fusions are not seen

N • Background Sensitivity: ossification delay of the long bones is not seen in mice on a mixed background containing C57BL/6, C3H/HeN, DBA/1 or BALB/c unlike mice on a mixed background containing CBA/Ca

vision/eye

vision/eye phenotype ( J:89223 )

N • Background Sensitivity: unlike in mice on a mixed background containing C57BL/6 or CBA/Ca anophthalmia or microphthalmia are not seen