Phenotypes associated with this allele

• Allele Symbol: Otx2^tm1Sia
• Allele Name: targeted mutation 1, Shinichi Aizawa
• Allele ID: MGI:1857543
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Otx2^tm1Sia/Otx2^tm1Sia	involves: C57BL/6 * CBA	MGI:2167129
ht2	Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:2172552
ht3	Otx2^tm1Sia/Otx2^tm4Sia	involves: C57BL/6 * CBA	MGI:2178998
ht4	Otx2^tm1Sia/Otx2^tm4.1Sia	involves: C57BL/6 * CBA * FVB/N	MGI:3784196
ht5	Otx2^tm1Sia/Otx2^tm9Sia	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:5608498
ht6	Otx2^tm1Sia/Otx2^tm6Sia	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:3046979
ht7	Otx2^tm1Sia/Otx2^tm5Sia	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:3047000
ht8	Otx2^tm1Sia/Otx2^tm10Sia	involves: C57BL/6NCrlj * CBA/JNCrlj	MGI:5608500
cx9	Emx2^tm1Sia/Emx2^+ Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:3624427
cx10	Rr103^tm3Sia/Rr103^tm3Sia Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:4830713
cx11	Rr103^tm3.1Sia/Rr103^tm3.1Sia Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:4830716
cx12	Emx1^tm1Sia/Emx1^tm1Sia Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:3580107
cx13	Otx1^tm1Sia/Otx1^+ Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:3579861
cx14	Emx2^tm1Sia/Emx2^tm1Sia Otx2^tm1Sia/Otx2^+	involves: C57BL/6 * CBA	MGI:2172525

Genotype
MGI:2167129

hm1

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

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:29682 )

• homozygous embryos are not found beyond E10

embryo

abnormal gastrulation ( J:51989 )

• about half of embryos undergo abnormal gastrulation, exhibiting a characteristic constriction at the junction of the extraembryonic and embryonic ectoderm at early to mid-streak stage

abnormal mesendoderm development ( J:51989 )

• Hnf3beta-positive anterior mesendoderm does not form

rostral body truncation ( J:29682 )

• neuroaxis is rostrally truncated at the level of rostral to rhombomere 3, lacking all of the anterior structures including forebrain and midbrain

embryonic growth arrest ( J:29682 )

• growth is markedly retarded at E8.5

nervous system

abnormal brain development ( J:51989 )

• never develop regions anterior to rhomobomere 3

absent midbrain ( J:29682 )

• lack the midbrain

absent forebrain ( J:29682 )

• lack the forebrain

cardiovascular system

absent heart ( J:29682 )

• heart is absent at E8.5

digestive/alimentary system

absent foregut ( J:29682 )

• foregut is absent at E8.5

growth/size/body

abnormal anterior head development ( J:29682 )

• structures corresponding to the rostral head are absent at E8.5

Genotype
MGI:2172552

ht2

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

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:29682 , 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)

• 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)

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:29682 , 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)

• 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)

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:29682 , J:51989 )

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

Genotype
MGI:2178998

ht3

• Allelic Composition: Otx2^tm1Sia/Otx2^tm4Sia
• Genetic Background: involves: C57BL/6 * CBA

embryo

embryo phenotype ( J:74631 )

N • anterior visceral endoderm (AVE) and anterior definitive endoderm (ADE) form normally in mutants

N • anterior axial mesendoderm functions normally in mutants

open neural tube ( J:74631 )

• at 10.5 dpc, neural tube has failed to close

craniofacial

abnormal cranium morphology ( J:74631 )

• most skull elements in premandibular and distal components of mandibular regions develop although morphology is distorted

skeleton

abnormal cranium morphology ( J:74631 )

• most skull elements in premandibular and distal components of mandibular regions develop although morphology is distorted

nervous system

abnormal midbrain morphology ( J:74631 )

• the mesencephalon is malformed

absent diencephalon ( J:74631 )

• at 10.5 dpc, absence of diencephalon is noted

abnormal metencephalon morphology ( J:74631 )

• the rostral portion of metencephalic regions, including the isthmus, appears to be malformed

abnormal nervous system development ( J:74631 )

• neural plate loses competence to inductive signals from anterior neural ridge

open neural tube ( J:74631 )

• at 10.5 dpc, neural tube has failed to close

abnormal brain development ( J:74631 )

• at 10.5 dpc, rostral aspect of brain appears truncated

• majority of rostral brain fails to develop normally at 10.5 days post-coitum (dpc)

absent embryonic telencephalon ( J:74631 )

• at 10.5 dpc, absence of telencephalic vesicles is noted

abnormal midbrain-hindbrain boundary morphology ( J:74631 )

• the isthmus appears to be malformed

anencephaly ( J:74631 )

• at E18.5 all embryos exhibit exencephaly or anencephaly

exencephaly ( J:74631 )

• at E18.5 all embryos exhibit exencephaly or anencephaly

Genotype
MGI:3784196

ht4

• Allelic Composition: Otx2^tm1Sia/Otx2^tm4.1Sia
• Genetic Background: involves: C57BL/6 * CBA * FVB/N

normal phenotype

no abnormal phenotype detected ( J:74631 )

• viable with no apparent abnormalities

Genotype
MGI:5608498

ht5

• Allelic Composition: Otx2^tm1Sia/Otx2^tm9Sia
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

nervous system

abnormal embryonic neuroepithelium morphology ( J:207608 )

• diencephalic and mesencephalic regions are reduced

• reduction is more severe than in mice homozygous for Otx2^tm9Sia

abnormal forebrain morphology ( J:207608 )

• small telencephalic vesicle at E9.5

• reduction is more severe than in mice homozygous for Otx2^tm9Sia

embryo

abnormal embryonic neuroepithelium morphology ( J:207608 )

• diencephalic and mesencephalic regions are reduced

• reduction is more severe than in mice homozygous for Otx2^tm9Sia

Genotype
MGI:3046979

ht6

• Allelic Composition: Otx2^tm1Sia/Otx2^tm6Sia
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

nervous system

abnormal brain development ( J:91011 )

• midbrain and forebrain development is impaired

• defects are similar but milder compared to those in Otx2^tm1Sia and Otx2^tm5Sia compound heterozygous mutants

Genotype
MGI:3047000

ht7

• Allelic Composition: Otx2^tm1Sia/Otx2^tm5Sia
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

nervous system

abnormal brain development ( J:91011 )

• midbrain and forebrain development is impaired however the telencephalon appears normal

• at E15.5 the cerebellar primordium is expanded and the Fgf8 positive isthmic stripe is shifted rostrally

absent midbrain ( J:91011 )

• the midbrain is nearly absent

absent diencephalon ( J:91011 )

• the diencephalon is mostly absent

Genotype
MGI:5608500

ht8

• Allelic Composition: Otx2^tm1Sia/Otx2^tm10Sia
• Genetic Background: involves: C57BL/6NCrlj * CBA/JNCrlj

nervous system

abnormal embryonic neuroepithelium morphology ( J:207608 )

• diencephalic and mesencephalic regions are reduced

• phenotype is variable with the most severely affected embryos lacking almost the entire anterior neuroectoderm

abnormal forebrain morphology ( J:207608 )

• small telencephalic vesicle at E9.5

• reduction is more severe than in mice homozygous for Otx2^tm10Sia

embryo

abnormal embryonic neuroepithelium morphology ( J:207608 )

• diencephalic and mesencephalic regions are reduced

• phenotype is variable with the most severely affected embryos lacking almost the entire anterior neuroectoderm

Genotype
MGI:3624427

cx9

• Allelic Composition: Emx2^tm1Sia/Emx2⁺; Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

nervous system

abnormal forebrain morphology ( J:70745 )

• display defects in forebrain structures similar to, but significantly milder than, homozygous Emx2 and heterozygous Otx2 double mutants

Genotype
MGI:4830713

cx10

• Allelic Composition: Rr103^tm3Sia/Rr103^tm3Sia; Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

nervous system

absent diencephalon ( J:163926 )

• at E8.5, mice exhibit a loss of diencephalic structures compared with wild-type mice

Genotype
MGI:4830716

cx11

• Allelic Composition: Rr103^tm3.1Sia/Rr103^tm3.1Sia; Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

nervous system

absent diencephalon ( J:163926 )

• at E8.5, mice exhibit a loss of diencephalic structures compared with wild-type mice

Genotype
MGI:3580107

cx12

• Allelic Composition: Emx1^tm1Sia/Emx1^tm1Sia; Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

nervous system

nervous system phenotype ( J:98539 )

N • do not exhibit defects in the forebrain at E12.5

Genotype
MGI:3579861

cx13

• Allelic Composition: Otx1^tm1Sia/Otx1⁺; Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

prenatal lethality, complete penetrance ( J:73592 )

• no double heterozygous mutants are live-born

nervous system

abnormal nervous system morphology ( J:73592 )

• the medial longitudinal fasciculus is diminished

abnormal brain development ( J:51989 )

• at E10.5, the region between the otic vesicle and the isthmic constriction is enlarged, whereas that between the constriction and the sulcus telodiencephalicus is shortened

abnormal midbrain-hindbrain boundary morphology ( J:51989 )

• the isthmic constriction is not distinct

abnormal rhombic lip morphology ( J:73592 )

• expanded rhombic lip

abnormal posterior commissure morphology ( J:73592 )

• the posterior commissure is poorly fasciculated

abnormal midbrain morphology ( J:51989 , J:73592 )

• the midbrain is vestigial (J:51989)

• major nuclei in the mesencephalon such as the red nucleus and the oculomotor nucleus are present only as remnants in severe cases (J:73592)

decreased midbrain size ( J:73592 )

• reduced midbrain size

enlarged cerebral aqueduct ( J:73592 )

• greatly expanded aqueduct mesencephali

abnormal inferior colliculus morphology ( J:73592 )

• poorly developed

abnormal superior colliculus morphology ( J:73592 )

• poorly developed

abnormal oculomotor nucleus morphology ( J:73592 )

• the oculomotor nucleus is present only as a remnant in severe cases

abnormal pretectal region morphology ( J:51989 )

• the pretectum is vestigal

abnormal tegmentum morphology ( J:73592 )

• poorly developed

abnormal red nucleus morphology ( J:73592 )

• the red nucleus is present only as a remnant in severe cases

abnormal trigeminal V mesencephalic nucleus morphology ( J:73592 )

• axonal morphology of mesencephalic neurons is more disturbed than in Otx1 homozygotes

abnormal forebrain morphology ( J:51989 )

• invagination of the sulcus telodiencephalicus is poor

decreased substantia nigra size ( J:73592 )

• present only as a remnant in severe cases

abnormal diencephalon morphology ( J:73592 )

• decreased in size

• abnormal fasciculation and axonal pathway of the mammillothalamic tract

• the habenulopeduncular tract is meager, the axonal pathway is disturbed, and in severe cases, the tract is vestigial

abnormal hypothalamus morphology ( J:73592 )

• in severe cases, the hypothalamus is poorly developed

abnormal mammillary body morphology ( J:73592 )

• in severe cases, the mammillary body is poorly developed

small thalamus ( J:51989 , J:73592 )

• the thalamus is vestigial (J:51989)

• in severe cases, the ventral thalamus is poorly developed (J:73592)

abnormal telencephalon morphology ( J:51989 , J:73592 )

• smaller telencephalon (J:51989)

• abnormalities, especially in the dorsal part of the telencelphalon and in severe cases, no differentiation of the telencephalon was detected (J:73592)

abnormal cerebral hemisphere morphology ( J:51989 )

• cerebral hemispheres are mildly reduced in size

small hippocampus ( J:51989 , J:73592 )

• reduced size of hippocampal region and is even lacking in severe cases (J:73592)

abnormal cerebral cortex morphology ( J:73592 )

• cerebral cortical layers are poorly differentiated, the cortical plate and the ventricular zone are very narrow and the intermediate zone is expanded

small olfactory bulb ( J:73592 )

• olfactory bulb and septum are somewhat smaller in severely affected embryos but organization is normal

abnormal metencephalon morphology ( J:51989 )

• the anterior hindbrain is expanded

increased pons size ( J:51989 )

• the pons is expanded

enlarged cerebellum ( J:51989 , J:73592 )

• expanded cerebellum in severe cases (J:73592)

abnormal oculomotor nerve morphology ( J:73592 )

• oculomotor nerves emerge but are poorly fasciculated

abnormal optic nerve morphology ( J:73592 )

• ophthalmic branch is poorly fasciculated and even lost in severe cases, however the mandibular and maxillary branches develop normally

abnormal trochlear nerve morphology ( J:73592 )

• trochlear nerves emerge but are poorly fasciculated

skeleton

abnormal cranium morphology ( J:73592 )

• alicochlear commissure has several extra cartilage branches

abnormal sphenoid bone morphology ( J:73592 )

basisphenoid bone foramen ( J:73592 )

• basisphenoid has a single foramen

abnormal orbitosphenoid bone morphology ( J:73592 )

• incomplete ossification of the oribitosphenoid

presphenoid bone hypoplasia ( J:73592 )

• poorly developed presphenoid

abnormal cartilage morphology ( J:73592 )

• alicochlear commissure has several extra cartilage branches

craniofacial

abnormal cranium morphology ( J:73592 )

• alicochlear commissure has several extra cartilage branches

abnormal sphenoid bone morphology ( J:73592 )

basisphenoid bone foramen ( J:73592 )

• basisphenoid has a single foramen

abnormal orbitosphenoid bone morphology ( J:73592 )

• incomplete ossification of the oribitosphenoid

presphenoid bone hypoplasia ( J:73592 )

• poorly developed presphenoid

vision/eye

abnormal orbitosphenoid bone morphology ( J:73592 )

• incomplete ossification of the oribitosphenoid

abnormal optic nerve morphology ( J:73592 )

• ophthalmic branch is poorly fasciculated and even lost in severe cases, however the mandibular and maxillary branches develop normally

Genotype
MGI:2172525

cx14

• Allelic Composition: Emx2^tm1Sia/Emx2^tm1Sia; Otx2^tm1Sia/Otx2⁺
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:70745 )

• none survive beyond E16.5

nervous system

abnormal olfactory sensory neuron morphology ( J:70745 )

• olfactory neurons do not project to the olfactory bulb, rather the nerve fibers are tangled outside the bulb

abnormal midbrain-hindbrain boundary morphology ( J:70745 )

• isthmic constriction is shifted rostrally

absent choroid plexus ( J:70745 , J:98539 )

• the choroid plexus does not develop in the third ventricle at E15.5 (J:70745)

• choroid plexus fails to develop at E12.5 (J:98539)

abnormal posterior commissure morphology ( J:70745 )

• the posterior commissure is located proximal to the sulcus telodiencephalicus and is reduced in size and poorly fasciculated

abnormal anterior commissure morphology ( J:70745 )

• exhibit no axonal fasciculation of the anterior commissure

abnormal midbrain morphology ( J:70745 )

• anterior boundary of the mesencephalon is poorly differentiated

enlarged tectum ( J:70745 )

• the tectum is greatly enlarged occupying the original epithalamus and pretectum regions

abnormal pretectal region morphology ( J:70745 )

• the anterior pretectum is not apparent

abnormal forebrain morphology ( J:70745 )

• severe defects in dorsal forebrain

abnormal adenohypophysis morphology ( J:70745 )

• the adenohypophysis (the anterior glandular lobe) is irregularly shaped

abnormal forebrain development ( J:163926 )

• the thalamic eminence, ventral thalamus (prethalamus), dorsal thalamus (thalamus), and noncommissure regions of the pretectum fail to develop unlike in wild-type mice

abnormal thalamus morphology ( J:70745 )

• prethalamus and the dorsal and ventral thalamus are not apparent

abnormal telencephalon morphology ( J:70745 , J:98539 )

• cerebral hemispheres are greatly diminished in the telencephalon (J:70745)

• at E12.5, the telencephalon is small and diminished, particularly in the dorsomedial aspect, resulting in an enlarged and exposed telencephalic roof (J:70745)

• evagination of the the medial telencephalic pallium beyond the sulcus telodiencephalicus is poor (J:70745)

• eminentia thalami fails to develop at E12.5, however the rostral forebrain territory of ganglionic eminences, neopallium and commissural plate develop (J:98539)

• the choroidal roof at the telencephalic level fails to develop at E12.5 (J:98539)

abnormal corpus callosum morphology ( J:70745 )

• exhibit no axonal fasciculation of the corpus callosum

abnormal Ammon gyrus morphology ( J:70745 )

• Ammon's horn is not apparent at E12.5

absent dentate gyrus ( J:70745 )

• dentate gyrus is not formed at E15.5

absent hippocampal fimbria ( J:70745 )

• the fimbria are not formed at E15.5

• exhibit no axonal fasciculation of the fimbria

abnormal hippocampal fornix morphology ( J:70745 )

• exhibit no axonal fasciculation of the fornix

abnormal hippocampus region morphology ( J:70745 )

• the CA fields are not formed at E15.5

absent hippocampus ( J:70745 , J:98539 )

• hippocampal structures are entirely absent at E15.5 (J:70745)

• prospective hippocampus is absent at E12.5 (J:98539)

abnormal cerebral cortex morphology ( J:70745 , J:98539 )

• the neopallium is reduced with a disorganized laminar structure and the cortical plate is hardly visible (J:70745)

• the choroidal roof is expanded (J:70745)

• the archipallium and cortical hem fail to develop at E12.5 (J:98539)

abnormal olfactory bulb mitral cell layer morphology ( J:70745 )

• mitral cell layers are absent

small olfactory bulb ( J:70745 )

• small olfactory bulb that lacks the layered structure at E12.5

abnormal lateral ganglionic eminence morphology ( J:70745 )

• hyperplastic

abnormal medial ganglionic eminence morphology ( J:70745 )

• hyperplastic

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:70745 )

• the adenohypophysis (the anterior glandular lobe) is irregularly shaped

vision/eye

abnormal lens morphology ( J:70745 )

• irregularly shaped lenses

retina hyperplasia ( J:70745 )

• outer/inner layers of the retina are hyperplastic

craniofacial

abnormal olfactory sensory neuron morphology ( J:70745 )

• olfactory neurons do not project to the olfactory bulb, rather the nerve fibers are tangled outside the bulb

respiratory system

abnormal olfactory sensory neuron morphology ( J:70745 )

• olfactory neurons do not project to the olfactory bulb, rather the nerve fibers are tangled outside the bulb

taste/olfaction

abnormal olfactory sensory neuron morphology ( J:70745 )

• olfactory neurons do not project to the olfactory bulb, rather the nerve fibers are tangled outside the bulb

growth/size/body

abnormal olfactory sensory neuron morphology ( J:70745 )

• olfactory neurons do not project to the olfactory bulb, rather the nerve fibers are tangled outside the bulb