Phenotypes Associated with This Genotype

Genotype
MGI:3029251

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

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

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