Phenotypes associated with this allele

• Allele Symbol: Cdon^tm2Rsk
• Allele Name: targeted mutation 2, Robert S Krauss
• Allele ID: MGI:2653132
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdon^tm2Rsk/Cdon^tm2Rsk	B6.129-Cdon^tm2Rsk	MGI:3711333
hm2	Cdon^tm2Rsk/Cdon^tm2Rsk	involves: 129/Sv * C57BL/6	MGI:2653135
cx3	Cdon^tm2Rsk/Cdon^+ Gas1^tm2Fan/Gas1^tm2Fan	involves: 129 * C57BL/6J	MGI:3711887
cx4	Cdon^tm2Rsk/Cdon^tm2Rsk Gas1^tm2Fan/Gas1^tm2Fan	involves: 129 * C57BL/6J	MGI:3711883
cx5	Cdon^tm2Rsk/Cdon^tm2Rsk Gas1^tm2Fan/Gas1^+	involves: 129 * C57BL/6J	MGI:3711888

Genotype
MGI:3711333

hm1

• Allelic Composition: Cdon^tm2Rsk/Cdon^tm2Rsk
• Genetic Background: B6.129-Cdon^tm2Rsk

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

mortality/aging

premature death ( J:109070 )

• 15 to 20% do not exhibit overt signs of holoprosencephaly and survive beyond the perinatal period, but die within 4-12 weeks of birth

perinatal lethality, incomplete penetrance ( J:109070 )

• homozygotes that develop holoprosencephaly (80-85%) die perinatally

nervous system

abnormal neuronal precursor proliferation ( J:109070 )

• primary neural progenitor cells from E14.5 cortices display a reduced proliferation rate

absent lamina terminalis ( J:109070 )

• the dorsal midline of cortices exhibit an abnormal structure, lacking the lamina terminalis

holoprosencephaly ( J:109070 )

• 80-85% develop severe forms of holoprosencephaly

hydrocephaly ( J:109070 )

• mutants that survive the postnatal period develop hydroencephaly

abnormal brain ventricle morphology ( J:109070 )

abnormal forebrain morphology ( J:109070 )

• mutants that survive the postnatal period exhibit highly enlarged forebrains with dilated blood vessels and olfactory bulbs

• mutants that survive the postnatal period exhibit an enlarged gap between the hypothalamus and pons, indicating a slight truncation of the forebrain

enlarged lateral ventricles ( J:109070 )

• mutants that survive the postnatal period have enlarged lateral ventricles with a disruption of the septum, consistent with hydrocephalus

abnormal cerebral cortex morphology ( J:109070 )

• the dorsal midline of cortices exhibit an abnormal structure, lacking the lamina terminalis

thin cerebral cortex ( J:109070 )

• the posterior telencephalon of E18.5 brains shows a translucent appearance, indicating thinning of the cortex

• variable severity of cortical thinning; mutants with holoprosencephaly exhibit the most severe thinning

craniofacial

domed cranium ( J:109070 )

• mutants that survive the postnatal period have a dome-shaped head

cardiovascular system

abnormal blood vessel morphology ( J:109070 )

• dilated blood vessels in the enlarged forebrain

hemorrhage ( J:109070 )

• mutants that survive the postnatal period have brains that display surface bleeding

behavior/neurological

weakness ( J:109070 )

• mutants that survive the postnatal period show limb weakness and immobility

skeleton

domed cranium ( J:109070 )

• mutants that survive the postnatal period have a dome-shaped head

cellular

abnormal neuronal precursor proliferation ( J:109070 )

• primary neural progenitor cells from E14.5 cortices display a reduced proliferation rate

embryo

absent lamina terminalis ( J:109070 )

• the dorsal midline of cortices exhibit an abnormal structure, lacking the lamina terminalis

Genotype
MGI:2653135

hm2

• Allelic Composition: Cdon^tm2Rsk/Cdon^tm2Rsk
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:82221 )

• exhibit a similar range and frequency of neonatal lethality as Cdon^tm1Rsk homozygotes

postnatal lethality, incomplete penetrance ( J:82221 )

• exhibit a similar range and frequency of lethality as Cdon^tm1Rsk homozygotes

growth/size/body

abnormal upper incisor morphology ( J:82221 )

• mutants either have a single, central maxillary incisor or no maxillary incisors

absent upper incisors ( J:82221 )

• maxillary incisors are sometimes absent

abnormal philtrum morphology ( J:82221 )

• dysgenesis of the philtrum

absent primary palate ( J:82221 )

• lack a primary palate

abnormal nose morphology ( J:82221 )

• increase in presumptive mesenchyme between the nasal capsule and the oral cavity

• although medial nasal process (MNP) fusion occurs normally at E11.5, later stage embryos maintain an epithelialized furrow at the MNP midline and have a recessed inferior border

absent nasal septum cartilage ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

nasal septum cartilage hypoplasia ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

small nasal septum ( J:82221 )

• nasal septum is reduced in size

piriform aperture stenosis ( J:82221 )

• fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

decreased body size ( J:82221 )

craniofacial

abnormal craniofacial morphology ( J:82221 )

• about 95% of mutants exhibit craniofacial abnormalities

basisphenoid bone foramen ( J:82221 )

small basisphenoid bone ( J:82221 )

abnormal upper incisor morphology ( J:82221 )

• mutants either have a single, central maxillary incisor or no maxillary incisors

absent upper incisors ( J:82221 )

• maxillary incisors are sometimes absent

abnormal premaxilla morphology ( J:82221 )

• fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

abnormal philtrum morphology ( J:82221 )

• dysgenesis of the philtrum

absent primary palate ( J:82221 )

• lack a primary palate

abnormal nose morphology ( J:82221 )

• increase in presumptive mesenchyme between the nasal capsule and the oral cavity

• although medial nasal process (MNP) fusion occurs normally at E11.5, later stage embryos maintain an epithelialized furrow at the MNP midline and have a recessed inferior border

absent nasal septum cartilage ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

nasal septum cartilage hypoplasia ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

small nasal septum ( J:82221 )

• nasal septum is reduced in size

piriform aperture stenosis ( J:82221 )

• fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

skeleton

basisphenoid bone foramen ( J:82221 )

small basisphenoid bone ( J:82221 )

abnormal upper incisor morphology ( J:82221 )

• mutants either have a single, central maxillary incisor or no maxillary incisors

absent upper incisors ( J:82221 )

• maxillary incisors are sometimes absent

abnormal premaxilla morphology ( J:82221 )

• fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

absent nasal septum cartilage ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

nasal septum cartilage hypoplasia ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

respiratory system

abnormal nose morphology ( J:82221 )

• increase in presumptive mesenchyme between the nasal capsule and the oral cavity

• although medial nasal process (MNP) fusion occurs normally at E11.5, later stage embryos maintain an epithelialized furrow at the MNP midline and have a recessed inferior border

absent nasal septum cartilage ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

nasal septum cartilage hypoplasia ( J:82221 )

• agenesis or hypoplasia of the nasal septal cartilage

small nasal septum ( J:82221 )

• nasal septum is reduced in size

piriform aperture stenosis ( J:82221 )

• fusion of the premaxillary bone, resulting in severe pyriform aperture stenosis

digestive/alimentary system

absent primary palate ( J:82221 )

• lack a primary palate

nervous system

holoprosencephaly ( J:82221 )

• microform holoprosencephaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:82221

Genotype
MGI:3711887

cx3

• Allelic Composition: Cdon^tm2Rsk/Cdon⁺; Gas1^tm2Fan/Gas1^tm2Fan
• Genetic Background: involves: 129 * C57BL/6J

limbs/digits/tail

hindlimb oligodactyly ( J:121553 )

• digit 2 or 3 is complete absent form hindlimbs

syndactyly ( J:121553 )

• forelimb digits 2 and 3 are fused

Genotype
MGI:3711883

cx4

• Allelic Composition: Cdon^tm2Rsk/Cdon^tm2Rsk; Gas1^tm2Fan/Gas1^tm2Fan
• Genetic Background: involves: 129 * C57BL/6J

limbs/digits/tail

abnormal limb morphology ( J:121553 )

• limb defects resemble those seen in Gas1^tm2Fan homozygotes

craniofacial

abnormal craniofacial morphology ( J:121553 )

• more significant than defects seen in Gas1^tm2Fan/Gas1^tm2Fan Shh^tm1Chg/Shh⁺homozygotes

absent mandible ( J:121553 )

absent maxilla ( J:121553 )

abnormal face development ( J:121553 )

• medial facial structures are completely lacking

abnormal nose morphology ( J:121553 )

• nasal process defects

nervous system

holoprosencephaly ( J:121553 )

skeleton

absent mandible ( J:121553 )

absent maxilla ( J:121553 )

abnormal vertebrae morphology ( J:121553 )

• ventral medial components are absent

cervical vertebral fusion ( J:121553 )

abnormal vertebral body morphology ( J:121553 )

• lack of ossification

respiratory system

abnormal nose morphology ( J:121553 )

• nasal process defects

growth/size/body

abnormal face development ( J:121553 )

• medial facial structures are completely lacking

abnormal nose morphology ( J:121553 )

• nasal process defects

Genotype
MGI:3711888

cx5

• Allelic Composition: Cdon^tm2Rsk/Cdon^tm2Rsk; Gas1^tm2Fan/Gas1⁺
• Genetic Background: involves: 129 * C57BL/6J

limbs/digits/tail

hindlimb oligodactyly ( J:121553 )

• digit 2 or 3 is complete absent form hindlimbs

syndactyly ( J:121553 )

• forelimb digits 2 and 3 are fused

skeleton

abnormal vertebral body morphology ( J:121553 )

• lack of ossification