Phenotypes Associated with This Genotype

Genotype
MGI:5000245

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

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

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