Phenotypes associated with this allele

• Allele Symbol: Cdon^tm1Rsk
• Allele Name: targeted mutation 1, Robert S Krauss
• Allele ID: MGI:2653120
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdon^tm1Rsk/Cdon^tm1Rsk	B6.129-Cdon^tm1Rsk	MGI:3711318
hm2	Cdon^tm1Rsk/Cdon^tm1Rsk	involves: 129/Sv * 129S6/SvEvTac	MGI:5000249
hm3	Cdon^tm1Rsk/Cdon^tm1Rsk	involves: 129/Sv * C57BL/6	MGI:2653134
cx4	Boc^tm1Rsk/Boc^tm1Rsk Cdon^tm1Rsk/Cdon^tm1Rsk	B6.129-Boc^tm1Rsk Cdon^tm1Rsk	MGI:5000248
cx5	Boc^tm2Rsk/Boc^tm2Rsk Cdon^tm1Rsk/Cdon^tm1Rsk	B6.129-Boc^tm2Rsk Cdon^tm1Rsk	MGI:5000247
cx6	Boc^tm1Rsk/Boc^+ Cdon^tm1Rsk/Cdon^tm1Rsk	involves: 129/Sv * 129S6/SvEvTac	MGI:5000244
cx7	Boc^tm2Rsk/Boc^tm2Rsk Cdon^tm1Rsk/Cdon^tm1Rsk	involves: 129/Sv * 129S6/SvEvTac	MGI:5000245
cx8	Boc^tm2Rsk/Boc^+ Cdon^tm1Rsk/Cdon^tm1Rsk	involves: 129/Sv * 129S6/SvEvTac	MGI:5000246
cx9	Boc^tm1Rsk/Boc^tm1Rsk Cdon^tm1Rsk/Cdon^tm1Rsk	involves: 129/Sv * 129S6/SvEvTac	MGI:5000243

Genotype
MGI:3711318

hm1

• Allelic Composition: Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: B6.129-Cdon^tm1Rsk

• ♀: 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:5000249

hm2

• Allelic Composition: Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac

craniofacial

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal craniofacial development ( J:171767 )

• midline defects in cranial bone patterning

• penetrance and severity are lower than in mice that also carry at least one copy of Bcmo1^tm1Rsk or Bcmo1^tm2Rsk

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in mice that also carry at least one copy of Bcmo1^tm1Rsk or Bcmo1^tm2Rsk

skeleton

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

digestive/alimentary system

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in mice that also carry at least one copy of Bcmo1^tm1Rsk or Bcmo1^tm2Rsk

growth/size/body

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in mice that also carry at least one copy of Bcmo1^tm1Rsk or Bcmo1^tm2Rsk

Genotype
MGI:2653134

hm3

• Allelic Composition: Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: involves: 129/Sv * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:82221 )

• some homozygotes die shortly after birth

postnatal lethality, incomplete penetrance ( J:82221 )

• about 60% die before P21

growth/size/body

abnormal upper incisor morphology ( J:82221 )

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

• however, maxillary molars and mandibular structures develop normally

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

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 )

• of the mutants that survive after birth, about 35% are runted

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

• however, maxillary molars and mandibular structures develop normally

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

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

respiratory system

abnormal nose morphology ( J:82221 )

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

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

• however, maxillary molars and mandibular structures develop normally

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

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:5000248

cx4

• Allelic Composition: Boc^tm1Rsk/Boc^tm1Rsk; Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: B6.129-Boc^tm1Rsk Cdon^tm1Rsk

nervous system

holoprosencephaly ( J:171767 )

• display a range of holoprosencephalic phenotypes

craniofacial

craniofacial phenotype ( J:171767 )

N • do not display cyclopia

cleft upper lip ( J:171767 )

• Background Sensitivity: unlike mice on a 129 background, mice on a C57BL/6 background display cleft lip

proboscis ( J:171767 )

• proboscis like nose

vision/eye

ocular hypotelorism ( J:171767 )

limbs/digits/tail

limbs/digits/tail phenotype ( J:171767 )

N • do not display digit patterning defects unlike Shh null mice

growth/size/body

cleft upper lip ( J:171767 )

• Background Sensitivity: unlike mice on a 129 background, mice on a C57BL/6 background display cleft lip

proboscis ( J:171767 )

• proboscis like nose

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:171767

Genotype
MGI:5000247

cx5

• Allelic Composition: Boc^tm2Rsk/Boc^tm2Rsk; Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: B6.129-Boc^tm2Rsk Cdon^tm1Rsk

nervous system

holoprosencephaly ( J:171767 )

• display a range of holoprosencephalic phenotypes

craniofacial

craniofacial phenotype ( J:171767 )

N • do not display cyclopia

cleft upper lip ( J:171767 )

• Background Sensitivity: unlike mice on a 129 background, mice on a C57BL/6 background display cleft lip

proboscis ( J:171767 )

• proboscis like nose

vision/eye

ocular hypotelorism ( J:171767 )

limbs/digits/tail

limbs/digits/tail phenotype ( J:171767 )

N • do not display digit patterning defects unlike Shh null mice

growth/size/body

cleft upper lip ( J:171767 )

• Background Sensitivity: unlike mice on a 129 background, mice on a C57BL/6 background display cleft lip

proboscis ( J:171767 )

• proboscis like nose

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:171767

Genotype
MGI:5000244

cx6

• Allelic Composition: Boc^tm1Rsk/Boc⁺; Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac

mortality/aging

preweaning lethality, incomplete penetrance ( J:171767 )

• slightly fewer than expected are recovered at P10

nervous system

holoprosencephaly ( J:171767 )

• penetrance and severity are lower than in double homozygotes

craniofacial

abnormal craniofacial morphology ( J:171767 )

• some embryos have craniofacial patterning defects as severe as those in double homozygous mice

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal craniofacial development ( J:171767 )

• midline defects in cranial bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal primary palate development ( J:171767 )

• malformed or missing

• penetrance is lower than in double homozygotes

abnormal secondary palate development ( J:171767 )

• malformed or open

abnormal upper lip morphology ( J:171767 )

• fused upper lip

• penetrance is lower than in double homozygotes

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

external nares atresia ( J:171767 )

• fused nostrils

• penetrance is lower than in double homozygotes

skeleton

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

respiratory system

external nares atresia ( J:171767 )

• fused nostrils

• penetrance is lower than in double homozygotes

digestive/alimentary system

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal primary palate development ( J:171767 )

• malformed or missing

• penetrance is lower than in double homozygotes

abnormal secondary palate development ( J:171767 )

• malformed or open

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

growth/size/body

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal primary palate development ( J:171767 )

• malformed or missing

• penetrance is lower than in double homozygotes

abnormal secondary palate development ( J:171767 )

• malformed or open

abnormal upper lip morphology ( J:171767 )

• fused upper lip

• penetrance is lower than in double homozygotes

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

external nares atresia ( J:171767 )

• fused nostrils

• penetrance is lower than in double homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:171767

Genotype
MGI:5000245

cx7

• Allelic Composition: Boc^tm2Rsk/Boc^tm2Rsk; Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac

mortality/aging

lethality during fetal growth through weaning, complete penetrance ( J:171767 )

• the expected numbers are recovered at E18.5 but no mice are recovered at P10

nervous system

holoprosencephaly ( J:171767 )

• strong midfacial holoprosencephaly defects with high penetrance at E11.5, E13.5, and E15.5

lobar holoprosencephaly ( J:171767 )

• relatively mild ventral forebrain midline defects similar to lobar holoprosencephaly

abnormal forebrain morphology ( J:171767 )

• relatively mild ventral forebrain midline defects similar to lobar holoprosencephaly

abnormal forebrain development ( J:171767 )

• display continuity across the ventral midline

• forebrain midline defect is less severe than in mice homozygous for Cdon^tm1Rsk alone on a C57BL/6 background

abnormal lateral ganglionic eminence morphology ( J:171767 )

• reduced in size or occasionally fused at E13.5

abnormal medial ganglionic eminence morphology ( J:171767 )

• reduced in size or occasionally fused at E13.5

craniofacial

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal craniofacial development ( J:171767 )

• hypoplasia at the facial midline at E11.5 with somewhat variable expressivity

• the most severe cases include fusion of the nasal processes at E11.5

• craniofacial defects are more severe than in mice homozygous for Cdon^tm1Rsk alone on a C57BL/6 background

• midline defects in cranial bone patterning

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

abnormal primary palate development ( J:171767 )

• malformed or missing

abnormal secondary palate development ( J:171767 )

• malformed or open

• at E13.5 palatal shelves usually grow medially towards each other rather than growing downward beside the tongue

failure of palatal shelf elevation ( J:171767 )

• at E14.5 palatal shelves either resemble those at E13.5 or if they have grown fail to elevate

abnormal palatal shelf fusion at midline ( J:171767 )

• at E15.5 palatal shelves begin to fuse but in some cases fusion appears to begin medially rather than at the tips, in other cases the tips fail to fuse as they do not align properly

abnormal upper lip morphology ( J:171767 )

• fused upper lip at E13.5 and E15.5

• Background Sensitivity: unlike mice on a congenic C57BL/6 background, mice do not display cleft lip

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

abnormal external nares morphology ( J:171767 )

• fused and pointed nostrils at E13.5 and E15.5

external nares atresia ( J:171767 )

• fused nostrils at E13.5 and E15.5

abnormal nasal septum morphology ( J:171767 )

• precartilage primordium is hypoplastic at E15.5

vision/eye

ocular hypotelorism ( J:171767 )

• at E13.5 and E15.5

skeleton

skeleton phenotype ( J:171767 )

N • limb skeletal development is not significantly different from controls

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal intervertebral disk development ( J:171767 )

• lack ossification of the cervical vertebrae intervertebral discs at E18.5

digestive/alimentary system

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

abnormal primary palate development ( J:171767 )

• malformed or missing

abnormal secondary palate development ( J:171767 )

• malformed or open

• at E13.5 palatal shelves usually grow medially towards each other rather than growing downward beside the tongue

failure of palatal shelf elevation ( J:171767 )

• at E14.5 palatal shelves either resemble those at E13.5 or if they have grown fail to elevate

abnormal palatal shelf fusion at midline ( J:171767 )

• at E15.5 palatal shelves begin to fuse but in some cases fusion appears to begin medially rather than at the tips, in other cases the tips fail to fuse as they do not align properly

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

respiratory system

abnormal external nares morphology ( J:171767 )

• fused and pointed nostrils at E13.5 and E15.5

external nares atresia ( J:171767 )

• fused nostrils at E13.5 and E15.5

abnormal nasal septum morphology ( J:171767 )

• precartilage primordium is hypoplastic at E15.5

growth/size/body

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

abnormal primary palate development ( J:171767 )

• malformed or missing

abnormal secondary palate development ( J:171767 )

• malformed or open

• at E13.5 palatal shelves usually grow medially towards each other rather than growing downward beside the tongue

failure of palatal shelf elevation ( J:171767 )

• at E14.5 palatal shelves either resemble those at E13.5 or if they have grown fail to elevate

abnormal palatal shelf fusion at midline ( J:171767 )

• at E15.5 palatal shelves begin to fuse but in some cases fusion appears to begin medially rather than at the tips, in other cases the tips fail to fuse as they do not align properly

abnormal upper lip morphology ( J:171767 )

• fused upper lip at E13.5 and E15.5

• Background Sensitivity: unlike mice on a congenic C57BL/6 background, mice do not display cleft lip

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

abnormal external nares morphology ( J:171767 )

• fused and pointed nostrils at E13.5 and E15.5

external nares atresia ( J:171767 )

• fused nostrils at E13.5 and E15.5

abnormal nasal septum morphology ( J:171767 )

• precartilage primordium is hypoplastic at E15.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:171767

Genotype
MGI:5000246

cx8

• Allelic Composition: Boc^tm2Rsk/Boc⁺; Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac

mortality/aging

preweaning lethality, incomplete penetrance ( J:171767 )

• slightly fewer than expected are recovered at P10

nervous system

holoprosencephaly ( J:171767 )

• penetrance and severity are lower than in double homozygotes

craniofacial

abnormal craniofacial morphology ( J:171767 )

• some embryos have craniofacial patterning defects as severe as those in double homozygous mice

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal craniofacial development ( J:171767 )

• midline defects in cranial bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal primary palate development ( J:171767 )

• malformed or missing

• penetrance is lower than in double homozygotes

abnormal secondary palate development ( J:171767 )

• malformed or open

abnormal upper lip morphology ( J:171767 )

• fused upper lip

• penetrance is lower than in double homozygotes

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

external nares atresia ( J:171767 )

• fused nostrils

• penetrance is lower than in double homozygotes

skeleton

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

digestive/alimentary system

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal primary palate development ( J:171767 )

• malformed or missing

• penetrance is lower than in double homozygotes

abnormal secondary palate development ( J:171767 )

• malformed or open

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

respiratory system

external nares atresia ( J:171767 )

• fused nostrils

• penetrance is lower than in double homozygotes

growth/size/body

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

• penetrance and severity are lower than in double homozygotes

abnormal primary palate development ( J:171767 )

• malformed or missing

• penetrance is lower than in double homozygotes

abnormal secondary palate development ( J:171767 )

• malformed or open

abnormal upper lip morphology ( J:171767 )

• fused upper lip

• penetrance is lower than in double homozygotes

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

external nares atresia ( J:171767 )

• fused nostrils

• penetrance is lower than in double homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:171767

Genotype
MGI:5000243

cx9

• Allelic Composition: Boc^tm1Rsk/Boc^tm1Rsk; Cdon^tm1Rsk/Cdon^tm1Rsk
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac

mortality/aging

lethality during fetal growth through weaning, complete penetrance ( J:171767 )

• the expected numbers are recovered at E18.5 but no mice are recovered at P10

nervous system

holoprosencephaly ( J:171767 )

• strong midfacial holoprosencephaly defects with high penetrance at E11.5, E13.5, and E15.5

lobar holoprosencephaly ( J:171767 )

• relatively mild ventral forebrain midline defects similar to lobar holoprosencephaly

abnormal forebrain morphology ( J:171767 )

• relatively mild ventral forebrain midline defects similar to lobar holoprosencephaly

abnormal forebrain development ( J:171767 )

• display continuity across the ventral midline

• forebrain midline defect is less severe than in mice homozygous for Cdon^tm1Rsk alone on a C57BL/6 background

abnormal lateral ganglionic eminence morphology ( J:171767 )

• reduced in size or occasionally fused at E13.5

abnormal medial ganglionic eminence morphology ( J:171767 )

• reduced in size or occasionally fused at E13.5

craniofacial

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal craniofacial development ( J:171767 )

• hypoplasia at the facial midline at E11.5 with somewhat variable expressivity

• the most severe cases include fusion of the nasal processes at E11.5

• craniofacial defects are more severe than in mice homozygous for Cdon^tm1Rsk alone on a C57BL/6 background

• midline defects in cranial bone patterning

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

abnormal primary palate development ( J:171767 )

• malformed or missing

abnormal secondary palate development ( J:171767 )

• malformed or open

• at E13.5 palatal shelves usually grow medially towards each other rather than growing downward beside the tongue

failure of palatal shelf elevation ( J:171767 )

• at E14.5 palatal shelves either resemble those at E13.5 or if they have grown fail to elevate

abnormal palatal shelf fusion at midline ( J:171767 )

• at E15.5 palatal shelves begin to fuse but in some cases fusion appears to begin medially rather than at the tips, in other cases the tips fail to fuse as they do not align properly

abnormal upper lip morphology ( J:171767 )

• fused upper lip at E13.5 and E15.5

• Background Sensitivity: unlike mice on a congenic C57BL/6 background, mice do not display cleft lip

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

abnormal external nares morphology ( J:171767 )

• fused and pointed nostrils at E13.5 and E15.5

external nares atresia ( J:171767 )

• fused nostrils at E13.5 and E15.5

abnormal nasal septum morphology ( J:171767 )

• precartilage primordium is hypoplastic at E15.5

vision/eye

ocular hypotelorism ( J:171767 )

• at E13.5 and E15.5

skeleton

skeleton phenotype ( J:171767 )

N • limb skeletal development is not significantly different from controls

basisphenoid bone foramen ( J:171767 )

small basisphenoid bone ( J:171767 )

abnormal maxilla morphology ( J:171767 )

• dysmorphic maxillary bones

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal premaxilla morphology ( J:171767 )

• fused premaxillary bones

abnormal intervertebral disk development ( J:171767 )

• lack ossification of the cervical vertebrae intervertebral discs at E18.5

respiratory system

abnormal external nares morphology ( J:171767 )

• fused and pointed nostrils at E13.5 and E15.5

external nares atresia ( J:171767 )

• fused nostrils at E13.5 and E15.5

abnormal nasal septum morphology ( J:171767 )

• precartilage primordium is hypoplastic at E15.5

digestive/alimentary system

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

abnormal primary palate development ( J:171767 )

• malformed or missing

abnormal secondary palate development ( J:171767 )

• malformed or open

• at E13.5 palatal shelves usually grow medially towards each other rather than growing downward beside the tongue

failure of palatal shelf elevation ( J:171767 )

• at E14.5 palatal shelves either resemble those at E13.5 or if they have grown fail to elevate

abnormal palatal shelf fusion at midline ( J:171767 )

• at E15.5 palatal shelves begin to fuse but in some cases fusion appears to begin medially rather than at the tips, in other cases the tips fail to fuse as they do not align properly

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

growth/size/body

abnormal maxillary shelf morphology ( J:171767 )

• absent or diminished maxillary shelves

absent maxillary shelf ( J:171767 )

decreased maxillary shelf size ( J:171767 )

abnormal palate development ( J:171767 )

• midline defects in palatal bone patterning

abnormal primary palate development ( J:171767 )

• malformed or missing

abnormal secondary palate development ( J:171767 )

• malformed or open

• at E13.5 palatal shelves usually grow medially towards each other rather than growing downward beside the tongue

failure of palatal shelf elevation ( J:171767 )

• at E14.5 palatal shelves either resemble those at E13.5 or if they have grown fail to elevate

abnormal palatal shelf fusion at midline ( J:171767 )

• at E15.5 palatal shelves begin to fuse but in some cases fusion appears to begin medially rather than at the tips, in other cases the tips fail to fuse as they do not align properly

abnormal upper lip morphology ( J:171767 )

• fused upper lip at E13.5 and E15.5

• Background Sensitivity: unlike mice on a congenic C57BL/6 background, mice do not display cleft lip

absent primary palate ( J:171767 )

• missing in some cases

cleft palate ( J:171767 )

• in some mice at E17.5

abnormal external nares morphology ( J:171767 )

• fused and pointed nostrils at E13.5 and E15.5

external nares atresia ( J:171767 )

• fused nostrils at E13.5 and E15.5

abnormal nasal septum morphology ( J:171767 )

• precartilage primordium is hypoplastic at E15.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 11		DOID:0110877	OMIM:614226	J:171767