Phenotypes Associated with This Genotype

Genotype
MGI:2172552

• Allelic Composition: Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:29682 )

• Background Sensitivity: many heterozygotes obtained from crosses of chimeras with CBA females survive the postnatal period and appear normal but die by the age of 2 months unlike those obtained from C57BL/6 matings which die shortly after birth

neonatal lethality, incomplete penetrance ( J:29682 )

• Background Sensitivity: most heterozygotes obtained from crosses of chimeras with C57BL/6 females die within 1 day after birth and exhibit head and eye malformations while crosses of chimeras with CBA females do not

• Background Sensitivity: all phenotypic data presented below is from heterozygotes obtained from crosses with C57BL/6 females and not from CBA crosses

vision/eye

abnormal eye morphology ( J:51989 )

• 53% of mutants mated to C57BL/6 have defects in the eyes

• approximately 17% show defects only in the eyes

absent orbitosphenoid bone ( J:29682 )

• mutants with short nose or acephaly usually lack the orbitosphenoid

abnormal extraocular muscle morphology ( J:29682 )

• extrinsic ocular muscles are deformed in mutants with microphthalmia

abnormal anterior eye segment morphology ( J:29682 )

aniridia ( J:29682 )

• mutants with microphthalmia often lack the iris

absent cornea ( J:29682 )

• mutants with microphthalmia often lack the cornea

aphakia ( J:29682 )

• mutants with microphthalmia often lack the lens

abnormal eye distance/ position ( J:29682 )

• mutants with microphthalmia often exhibit dislocated eyes, either protruding prominently over the surface of the face or deeply buried in the orbit

microphthalmia ( J:29682 )

• 16.7% exhibit microphthalmia

• 15.4% exhibit microphthalmia with micrognathia

abnormal eyelid morphology ( J:29682 )

• deformed eyelids are seen in some mutants with microphthalmia

abnormal retina layer morphology ( J:29682 )

• in mutants with microphthalmia, the retinal layers are hyperplastic

retina pigment epithelium hyperplasia ( J:29682 )

• in mutants with microphthalmia, the pigment epithelial layers are hyperplastic and sometimes folded several times within a single eyeball

abnormal sclera morphology ( J:29682 )

• the sclera is deformed in some mutants with microphthalmia

anophthalmia ( J:29682 )

• 37.8 % exhibit anophthalmia or microphthalmia with agnathia

• in mutants with anophthalmia, only a trace of pigmented cells is present with remnants of extrinsic eye muscles

skeleton

abnormal cranium morphology ( J:29682 )

• variable degree of skull abnormalities

• mutants with acephaly show no skull elements anterior to the alisphenoid, including dermal bones in the upper jaw

• the anterior portion of the skull is atrophic in mutants with holoprosencephaly

abnormal basisphenoid bone morphology ( J:29682 )

• mutants with holoprosencephaly display fused basisphenoid and presphenoid bones that are split into two halves along the midline

• mutants with micrognathia show fusion of the transverse bar of ectopic bone of the basisphenoid with pterygoid processes laterally

basisphenoid bone foramen ( J:29682 )

• mutants with microphthalmia or anophthalmia or with no external abnormalities display the presence of a single or a few foramina in the basisphenoid

abnormal Meckel's cartilage morphology ( J:29682 )

• in agnathia, Meckel's cartilage and malleus fuse in the midline forming a short transverse rod and incus cartilages are shifted medially

small cranium ( J:29682 )

• mutants with holoprosencephaly exhibit a smaller skull because all of the visceral skeletal elements are shifted medially

abnormal alisphenoid bone morphology ( J:29682 )

• in mutants with microphthalmia, the left incus is fused with alisphenoid

absent orbitosphenoid bone ( J:29682 )

• mutants with short nose or acephaly usually lack the orbitosphenoid

abnormal presphenoid bone morphology ( J:29682 )

• mutants with holoprosencephaly display fused basisphenoid and presphenoid bones that are split into two halves along the midline

abnormal pterygoid bone morphology ( J:29682 )

abnormal temporal bone tympanic part morphology ( J:29682 )

• the right and left tympanic bones are often fused in the middle

abnormal mandible morphology ( J:51989 , J:29682 )

• 53% of mutants mated to C57BL/6 have defects in the lower jaw (J:51989)

• approximately 6% show defects only in the lower jaw (J:51989)

• mutants with short nose exhibit variable deformation of the mandible (J:29682)

• mutants with micrognathia show mandibles that are fused in the middle and lack symphysis (J:29682)

absent mandibular coronoid process ( J:29682 )

• in severe cases, mutants with micrognathia show loss of the coronoid process

absent mandible ( J:29682 )

• 37.8 % exhibit microphthalmia or anophthalmia with agnathia

• mutants with holoprosencephaly or acephaly do not have a mandible

micrognathia ( J:29682 )

• 6.4% exhibit micrognathia

• 15.4% exhibit microphthalmia with micrognathia

• in micrognathia, the mandibular bones are fused to varying degrees

abnormal incus morphology ( J:29682 )

• in mutants with microphthalmia, the left incus is fused with alisphenoid

abnormal malleus morphology ( J:29682 )

• in mutants with agnathia, Meckel's cartilage and malleus fuse in the midline forming a short transverse rod

abnormal nasal capsule morphology ( J:29682 )

• mutants with micrognathia show asymmetric nasal capsule

• mutants with holoprosencephaly exhibit a nasal capsule that disappears into the median rod of cartilage

absent nasal capsule ( J:29682 )

• mutants with short nose or acephaly usually lack the nasal capsule

nervous system

abnormal vomeronasal organ morphology ( J:29682 )

• in severe cases, Jacobson's organ is greatly involuted or lacking entirely

absent vomeronasal organ ( J:29682 )

• in some severe cases

abnormal embryonic neuroepithelium morphology ( J:29682 )

• exhibit abnormalities in the cranial neuroepithelium at E10.5, showing a thinner neuroectoderm and a reduced number of mitotic cells in the mesencephalon

decreased embryonic neuroepithelium thickness ( J:29682 )

• thinner neuroectoderm at E10.5

abnormal adenohypophysis morphology ( J:29682 )

• the adenohypophysis in most mutants is deformed, with some lacking both the anterior and posterior lobes

abnormal ciliary ganglion morphology ( J:29682 )

• ciliary ganglion that originates in the mesencephalic neural crest is frequently affected and absent when eyes are heavily deformed

abnormal midbrain-hindbrain boundary morphology ( J:29682 )

• the constriction between the midbrain and hindbrain is obscured

ethmocephaly ( J:29682 )

• 2.6% exhibit ethmocephaly (holoprosencephaly)

absent choroid plexus ( J:29682 )

• in mutants with holoprosencephaly, the choroid plexus is absent at the telencephalon level

abnormal third ventricle morphology ( J:29682 )

• in mutants with holoprosencephaly, the third ventricle does not grow a pair of lateral ventricles but remains as an enlarged median vesicle

abnormal inferior colliculus morphology ( J:29682 )

• development of the inferior colliculus is frequently arrested

abnormal trigeminal V mesencephalic nucleus morphology ( J:29682 )

• the number of mesencephalic trigeminal neurons is greatly diminished and their axonal pathway is disturbed

absent midbrain ( J:29682 )

• entire midbrain is lost in mutants with acephaly

absent olfactory bulb ( J:29682 )

• the olfactory bulb is absent when the forebrain is heavily deformed

absent forebrain ( J:29682 )

• entire forebrain is lost mutants with acephaly

abnormal hindbrain morphology ( J:29682 )

• the rostral hindbrain is lacking in mutants with acephaly

• however, most of the hindbrain and spinal cord are present and normal

absent metencephalon ( J:29682 )

• the rostral hindbrain is lacking in mutants with acephaly

abnormal oculomotor nerve morphology ( J:29682 )

• oculomotor nerves frequently display anomalies such as poor fasciculation and dorsally directed axonal pathway

abnormal trigeminal nerve morphology ( J:29682 )

abnormal trochlear nerve morphology ( J:29682 )

• trochlear nerves frequently display anomalies such as poor fasciculation and dorsally directed axonal pathway

craniofacial

abnormal craniofacial morphology ( J:70745 )

• Background Sensitivity: heterozygotes obtained from crosses of chimeras with C57BL/6 females exhibit craniofacial defects while crosses of chimeras with CBA females do not

abnormal cranium morphology ( J:29682 )

• variable degree of skull abnormalities

• mutants with acephaly show no skull elements anterior to the alisphenoid, including dermal bones in the upper jaw

• the anterior portion of the skull is atrophic in mutants with holoprosencephaly

abnormal basisphenoid bone morphology ( J:29682 )

• mutants with holoprosencephaly display fused basisphenoid and presphenoid bones that are split into two halves along the midline

• mutants with micrognathia show fusion of the transverse bar of ectopic bone of the basisphenoid with pterygoid processes laterally

basisphenoid bone foramen ( J:29682 )

• mutants with microphthalmia or anophthalmia or with no external abnormalities display the presence of a single or a few foramina in the basisphenoid

abnormal Meckel's cartilage morphology ( J:29682 )

• in agnathia, Meckel's cartilage and malleus fuse in the midline forming a short transverse rod and incus cartilages are shifted medially

small cranium ( J:29682 )

• mutants with holoprosencephaly exhibit a smaller skull because all of the visceral skeletal elements are shifted medially

abnormal alisphenoid bone morphology ( J:29682 )

• in mutants with microphthalmia, the left incus is fused with alisphenoid

absent orbitosphenoid bone ( J:29682 )

• mutants with short nose or acephaly usually lack the orbitosphenoid

abnormal presphenoid bone morphology ( J:29682 )

• mutants with holoprosencephaly display fused basisphenoid and presphenoid bones that are split into two halves along the midline

abnormal pterygoid bone morphology ( J:29682 )

abnormal temporal bone tympanic part morphology ( J:29682 )

• the right and left tympanic bones are often fused in the middle

abnormal mandible morphology ( J:51989 , J:29682 )

• 53% of mutants mated to C57BL/6 have defects in the lower jaw (J:51989)

• approximately 6% show defects only in the lower jaw (J:51989)

• mutants with short nose exhibit variable deformation of the mandible (J:29682)

• mutants with micrognathia show mandibles that are fused in the middle and lack symphysis (J:29682)

absent mandibular coronoid process ( J:29682 )

• in severe cases, mutants with micrognathia show loss of the coronoid process

absent mandible ( J:29682 )

• 37.8 % exhibit microphthalmia or anophthalmia with agnathia

• mutants with holoprosencephaly or acephaly do not have a mandible

micrognathia ( J:29682 )

• 6.4% exhibit micrognathia

• 15.4% exhibit microphthalmia with micrognathia

• in micrognathia, the mandibular bones are fused to varying degrees

abnormal incus morphology ( J:29682 )

• in mutants with microphthalmia, the left incus is fused with alisphenoid

abnormal malleus morphology ( J:29682 )

• in mutants with agnathia, Meckel's cartilage and malleus fuse in the midline forming a short transverse rod

abnormal nasal capsule morphology ( J:29682 )

• mutants with micrognathia show asymmetric nasal capsule

• mutants with holoprosencephaly exhibit a nasal capsule that disappears into the median rod of cartilage

absent nasal capsule ( J:29682 )

• mutants with short nose or acephaly usually lack the nasal capsule

abnormal palate morphology ( J:29682 )

• mutants with acephaly do not contain a palate

absent tongue ( J:29682 )

• tongue is absent in some mutants with microphthalmia/anophthalmia with agnathia

abnormal nasal cavity morphology ( J:29682 )

• nasal cavities are deformed and have asymmetrical configuration in most mutants

abnormal nasal septum morphology ( J:29682 )

• in severe cases, the nasal septum is greatly involuted or lacking entirely

abnormal vomeronasal organ morphology ( J:29682 )

• in severe cases, Jacobson's organ is greatly involuted or lacking entirely

absent vomeronasal organ ( J:29682 )

• in some severe cases

absent nasal septum ( J:29682 )

• in some severe cases

abnormal olfactory epithelium morphology ( J:29682 )

• in severe cases, the olfactory epithelium is greatly involuted or lacking entirely

abnormal snout morphology ( J:29682 )

• severe atrophies of the snout are seen in mutants with holoprosencephaly, short nose, and acephaly

short snout ( J:29682 )

• 1.9% exhibit a short nose

hearing/vestibular/ear

abnormal incus morphology ( J:29682 )

• in mutants with microphthalmia, the left incus is fused with alisphenoid

abnormal malleus morphology ( J:29682 )

• in mutants with agnathia, Meckel's cartilage and malleus fuse in the midline forming a short transverse rod

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:29682 )

• the adenohypophysis in most mutants is deformed, with some lacking both the anterior and posterior lobes

digestive/alimentary system

abnormal palate morphology ( J:29682 )

• mutants with acephaly do not contain a palate

absent tongue ( J:29682 )

• tongue is absent in some mutants with microphthalmia/anophthalmia with agnathia

muscle

abnormal extraocular muscle morphology ( J:29682 )

• extrinsic ocular muscles are deformed in mutants with microphthalmia

pigmentation

retina pigment epithelium hyperplasia ( J:29682 )

• in mutants with microphthalmia, the pigment epithelial layers are hyperplastic and sometimes folded several times within a single eyeball

respiratory system

abnormal nasal capsule morphology ( J:29682 )

• mutants with micrognathia show asymmetric nasal capsule

• mutants with holoprosencephaly exhibit a nasal capsule that disappears into the median rod of cartilage

absent nasal capsule ( J:29682 )

• mutants with short nose or acephaly usually lack the nasal capsule

abnormal nasal cavity morphology ( J:29682 )

• nasal cavities are deformed and have asymmetrical configuration in most mutants

abnormal nasal septum morphology ( J:29682 )

• in severe cases, the nasal septum is greatly involuted or lacking entirely

abnormal vomeronasal organ morphology ( J:29682 )

• in severe cases, Jacobson's organ is greatly involuted or lacking entirely

absent vomeronasal organ ( J:29682 )

• in some severe cases

absent nasal septum ( J:29682 )

• in some severe cases

abnormal olfactory epithelium morphology ( J:29682 )

• in severe cases, the olfactory epithelium is greatly involuted or lacking entirely

absent nasopharynx ( J:29682 )

• nasopharynx is not formed in mutants with microphthalmia/anophthalmia plus agnathia

taste/olfaction

abnormal olfactory epithelium morphology ( J:29682 )

• in severe cases, the olfactory epithelium is greatly involuted or lacking entirely

embryo

abnormal embryonic neuroepithelium morphology ( J:29682 )

• exhibit abnormalities in the cranial neuroepithelium at E10.5, showing a thinner neuroectoderm and a reduced number of mitotic cells in the mesencephalon

decreased embryonic neuroepithelium thickness ( J:29682 )

• thinner neuroectoderm at E10.5

growth/size/body

abnormal nasal capsule morphology ( J:29682 )

• mutants with micrognathia show asymmetric nasal capsule

• mutants with holoprosencephaly exhibit a nasal capsule that disappears into the median rod of cartilage

absent nasal capsule ( J:29682 )

• mutants with short nose or acephaly usually lack the nasal capsule

abnormal palate morphology ( J:29682 )

• mutants with acephaly do not contain a palate

absent tongue ( J:29682 )

• tongue is absent in some mutants with microphthalmia/anophthalmia with agnathia

abnormal nasal cavity morphology ( J:29682 )

• nasal cavities are deformed and have asymmetrical configuration in most mutants

abnormal nasal septum morphology ( J:29682 )

• in severe cases, the nasal septum is greatly involuted or lacking entirely

abnormal vomeronasal organ morphology ( J:29682 )

• in severe cases, Jacobson's organ is greatly involuted or lacking entirely

absent vomeronasal organ ( J:29682 )

• in some severe cases

absent nasal septum ( J:29682 )

• in some severe cases

abnormal olfactory epithelium morphology ( J:29682 )

• in severe cases, the olfactory epithelium is greatly involuted or lacking entirely

abnormal snout morphology ( J:29682 )

• severe atrophies of the snout are seen in mutants with holoprosencephaly, short nose, and acephaly

short snout ( J:29682 )

• 1.9% exhibit a short nose

acephaly ( J:51989 , J:29682 )

• 3.2% exhibit no head (acephaly) (J:29682)