Phenotypes associated with this allele

• Allele Symbol: Vax1^tm1Pgr
• Allele Name: targeted mutation 1, Peter Gruss
• Allele ID: MGI:1859922
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Vax1^tm1Pgr/Vax1^tm1Pgr	either: (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * NMRI)	MGI:3789904
hm2	Vax1^tm1Pgr/Vax1^tm1Pgr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7387082
cx3	Gas1^tm1Fan/Gas1^tm1Fan Vax1^tm1Pgr/Vax1^tm1Pgr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7387091

Genotype
MGI:3789904

hm1

• Allelic Composition: Vax1^tm1Pgr/Vax1^tm1Pgr
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * NMRI)

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

mortality/aging

lethality at weaning, incomplete penetrance ( J:58997 )

• most surviving homozygotes die at weaning due to inability to consume solid food

premature death ( J:58997 )

• some homozygotes may live up to several months when reared in isolation and fed soft food

perinatal lethality, incomplete penetrance ( J:58997 )

• Background Sensitivity: only 6% of pups recovered after birth from heterozygote matings are homozygous on the 129/NMRI hybrid background, whereas no homozygous pups are found after birth from heterozygote matings on the 129/C57BL/6 hybrid background

• expected Mendelian ratios are observed in litters at 7.5 to 18.5 days post-coitum (dpc)

skeleton

abnormal upper incisor morphology ( J:58997 )

• maxillary incisors are severely abnormal or fused

fused upper incisors ( J:58997 )

craniofacial

abnormal upper incisor morphology ( J:58997 )

• maxillary incisors are severely abnormal or fused

fused upper incisors ( J:58997 )

cleft palate ( J:58997 )

• all homozygotes show cleft palate

nervous system

abnormal forebrain development ( J:58997 )

• from 10.5 dpc, variably deficient growth of structures in the medial anterior forebrain (medial ganglionic eminence, preoptic area, and septum) is observed

abnormal telencephalon development ( J:58997 )

• some mutants display absence of growth of medioventral structures at 15 dpc; others growth recovery of dorsolateral structures fusing medially at 16.5 dpc

• all mutants display growth defects in basal telencephalon

holoprosencephaly ( J:58997 )

• some embryos have defective cleavage of dorsal forebrain into bilateral vesicles

abnormal corpus callosum morphology ( J:58997 )

• fibers are observed crossing the midline at the level of the corpus callosum only in mutants showing growth of telencephalic dorsolateral structures fusing medially at 16.5 dpc

abnormal anterior commissure morphology ( J:58997 )

• fibers are observed crossing the midline at the anterior commissure level only in mutants showing growth of telencephalic dorsolateral structures fusing medially at 16.5 dpc,

abnormal hypothalamus morphology ( J:58997 )

• at 16.5 dpc, preoptic area is absent

abnormal optic nerve morphology ( J:58997 )

• optic nerve differentiation is abnormal; from 12.5 dpc, optic recess remains along length of optic nerve

• optic nerve is surrounded by thickened epithelium ventrally and a thin pigmented epithelium dorsally at 12.5 dpc

• fibers of optic nerve are located ventrally to the thickened epithelium at 16.5dpc

abnormal optic nerve innervation ( J:58997 )

• at 16.5 dpc, nerves enter brain at a lateral hypothalamic level

absent optic chiasm ( J:58997 )

• at 16.5 dpc, optic chiasm is absent

digestive/alimentary system

cleft palate ( J:58997 )

• all homozygotes show cleft palate

vision/eye

abnormal optic nerve morphology ( J:58997 )

• optic nerve differentiation is abnormal; from 12.5 dpc, optic recess remains along length of optic nerve

• optic nerve is surrounded by thickened epithelium ventrally and a thin pigmented epithelium dorsally at 12.5 dpc

• fibers of optic nerve are located ventrally to the thickened epithelium at 16.5dpc

abnormal optic nerve innervation ( J:58997 )

• at 16.5 dpc, nerves enter brain at a lateral hypothalamic level

absent optic chiasm ( J:58997 )

• at 16.5 dpc, optic chiasm is absent

coloboma ( J:58997 )

growth/size/body

abnormal upper incisor morphology ( J:58997 )

• maxillary incisors are severely abnormal or fused

fused upper incisors ( J:58997 )

cleft palate ( J:58997 )

• all homozygotes show cleft palate

Genotype
MGI:7387082

hm2

• Allelic Composition: Vax1^tm1Pgr/Vax1^tm1Pgr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

craniofacial

abnormal cranium morphology ( J:257247 )

• several defects associated with neurocranial and splanchnocranial elements of the chondrocranium are observed from E12.5 to E17.5; defects are mostly found along the ventral midline and vary in severity between mice

• however, the dermatocranium appears normal

small cranium ( J:257247 )

• the skull is slightly smaller at E17.5

abnormal presphenoid bone morphology ( J:257247 )

• at E17.5, the presphenoid shows absence of the medial processes and variable hypoplasia of the body

absent presphenoid bone ( J:257247 )

• in some cases, the entire presphenoid bone is essentially absent

presphenoid bone hypoplasia ( J:257247 )

• at E17.5, the body of the presphenoid bone shows a variable level of hypoplasia

abnormal upper incisor morphology ( J:257247 )

• only a single median maxillary central incisor (SMMCI) is present at E12.5 and E17.5, whereas two maxillary incisor teeth are present in the craniofacial midline of wild-type controls

small mandible ( J:257247 )

• at E17.5, the mandible is slightly smaller but otherwise normal

abnormal maxilla morphology ( J:257247 )

• narrowing of the anterior maxillary incisor region at E12.5

maxillary shelf hypoplasia ( J:257247 )

• the palatal processes of the maxilla are hypoplastic

abnormal premaxilla morphology ( J:257247 )

• the body of the premaxilla exhibits a variable circular midline defect while the palatal shelves of the premaxilla are hypoplastic

maxillary retrognathia ( J:257247 )

• obvious retrusion in the maxillary region at E17.5

absent palatine bone horizontal plate ( J:257247 )

• in many cases, the palatine bone lacks palatal processes, exposing the underlying presphenoid bone

palatine bone hypoplasia ( J:257247 )

• the body of the palatine bone is hypoplastic

vomer bone hypoplasia ( J:257247 )

• the vomer is hypoplastic at E17.5

palatal shelves fail to meet at midline ( J:257247 )

• palatal shelves elevate above the tongue but fail to approximate toward the midline; this is likely due to a large midline cavity within the CNS, extending from the floor of the hypothalamus through the nasal cavity to the roof of the oral cavity

abnormal midface morphology ( J:257247 )

• at E11.5, the midface is significantly truncated as a result of deceased cell proliferation in the ventral forebrain neuroectoderm and frontonasal mesenchyme

• however, no differences are observed in the levels of cell death

midface hypoplasia ( J:257247 )

• obvious retrusion in the maxillary region at E17.5

cleft palate ( J:257247 )

• cleft palate is fully penetrant and associated with defects in the paired maxillary and palatine bones

• however, no significant changes are detected in epithelial or mesenchymal proliferation at E13.5 or in linear dimensions of the shelves at E14.5

abnormal vomeronasal cartilage morphology ( J:257247 )

• the paraseptal cartilages are hypoplastic at E17.5

abnormal nasal cavity morphology ( J:257247 )

• at E14.5, a large midline cavity originating from the embryonic forebrain is found beneath the floor of the hypothalamus and extends through the nasal cavity to expand this region and prevent approximation of the palatal shelves

• this structure separates the paired vomeronasal organs (VNOs)and is demarcated from the oral cavity by a thin layer of neuroectoderm in more posterior regions

• paired VNOs are present and situated medially adjacent to the widened nasal cavity

absent nasal septum ( J:257247 )

• the nasal septum is absent at E17.5

digestive/alimentary system

maxillary shelf hypoplasia ( J:257247 )

• the palatal processes of the maxilla are hypoplastic

absent palatine bone horizontal plate ( J:257247 )

• in many cases, the palatine bone lacks palatal processes, exposing the underlying presphenoid bone

palatine bone hypoplasia ( J:257247 )

• the body of the palatine bone is hypoplastic

palatal shelves fail to meet at midline ( J:257247 )

• palatal shelves elevate above the tongue but fail to approximate toward the midline; this is likely due to a large midline cavity within the CNS, extending from the floor of the hypothalamus through the nasal cavity to the roof of the oral cavity

cleft palate ( J:257247 )

• cleft palate is fully penetrant and associated with defects in the paired maxillary and palatine bones

• however, no significant changes are detected in epithelial or mesenchymal proliferation at E13.5 or in linear dimensions of the shelves at E14.5

embryo

abnormal frontonasal mesenchyme morphology ( J:257247 )

• at E11.5, cell proliferation is decreased in the frontonasal mesenchyme

endocrine/exocrine glands

abnormal pituitary gland morphology ( J:257247 )

• at E15.5, a duplicated pituitary gland extends through the cranial base into the oral cavity

growth/size/body

abnormal upper incisor morphology ( J:257247 )

• only a single median maxillary central incisor (SMMCI) is present at E12.5 and E17.5, whereas two maxillary incisor teeth are present in the craniofacial midline of wild-type controls

maxillary shelf hypoplasia ( J:257247 )

• the palatal processes of the maxilla are hypoplastic

absent palatine bone horizontal plate ( J:257247 )

• in many cases, the palatine bone lacks palatal processes, exposing the underlying presphenoid bone

palatine bone hypoplasia ( J:257247 )

• the body of the palatine bone is hypoplastic

palatal shelves fail to meet at midline ( J:257247 )

• palatal shelves elevate above the tongue but fail to approximate toward the midline; this is likely due to a large midline cavity within the CNS, extending from the floor of the hypothalamus through the nasal cavity to the roof of the oral cavity

abnormal midface morphology ( J:257247 )

• at E11.5, the midface is significantly truncated as a result of deceased cell proliferation in the ventral forebrain neuroectoderm and frontonasal mesenchyme

• however, no differences are observed in the levels of cell death

midface hypoplasia ( J:257247 )

• obvious retrusion in the maxillary region at E17.5

cleft palate ( J:257247 )

• cleft palate is fully penetrant and associated with defects in the paired maxillary and palatine bones

• however, no significant changes are detected in epithelial or mesenchymal proliferation at E13.5 or in linear dimensions of the shelves at E14.5

abnormal vomeronasal cartilage morphology ( J:257247 )

• the paraseptal cartilages are hypoplastic at E17.5

abnormal nasal cavity morphology ( J:257247 )

• at E14.5, a large midline cavity originating from the embryonic forebrain is found beneath the floor of the hypothalamus and extends through the nasal cavity to expand this region and prevent approximation of the palatal shelves

• this structure separates the paired vomeronasal organs (VNOs)and is demarcated from the oral cavity by a thin layer of neuroectoderm in more posterior regions

• paired VNOs are present and situated medially adjacent to the widened nasal cavity

absent nasal septum ( J:257247 )

• the nasal septum is absent at E17.5

abnormal frontonasal mesenchyme morphology ( J:257247 )

• at E11.5, cell proliferation is decreased in the frontonasal mesenchyme

nervous system

abnormal pituitary gland morphology ( J:257247 )

• at E15.5, a duplicated pituitary gland extends through the cranial base into the oral cavity

lobar holoprosencephaly ( J:257247 )

• at E12.5, lobar holoprosencephaly is associated with narrowing of the maxillary incisor region and a single median maxillary central incisor (SMMCI)

• however, the upper lip remains intact

decreased forebrain size ( J:257247 )

• at E11.5, the ventral forebrain region is significantly truncated

abnormal lateral ventricle morphology ( J:257247 )

• fusion of the lateral ventricles in the CNS at E16.5

respiratory system

abnormal vomeronasal cartilage morphology ( J:257247 )

• the paraseptal cartilages are hypoplastic at E17.5

abnormal nasal cavity morphology ( J:257247 )

• at E14.5, a large midline cavity originating from the embryonic forebrain is found beneath the floor of the hypothalamus and extends through the nasal cavity to expand this region and prevent approximation of the palatal shelves

• this structure separates the paired vomeronasal organs (VNOs)and is demarcated from the oral cavity by a thin layer of neuroectoderm in more posterior regions

• paired VNOs are present and situated medially adjacent to the widened nasal cavity

absent nasal septum ( J:257247 )

• the nasal septum is absent at E17.5

skeleton

abnormal cranium morphology ( J:257247 )

• several defects associated with neurocranial and splanchnocranial elements of the chondrocranium are observed from E12.5 to E17.5; defects are mostly found along the ventral midline and vary in severity between mice

• however, the dermatocranium appears normal

small cranium ( J:257247 )

• the skull is slightly smaller at E17.5

abnormal presphenoid bone morphology ( J:257247 )

• at E17.5, the presphenoid shows absence of the medial processes and variable hypoplasia of the body

absent presphenoid bone ( J:257247 )

• in some cases, the entire presphenoid bone is essentially absent

presphenoid bone hypoplasia ( J:257247 )

• at E17.5, the body of the presphenoid bone shows a variable level of hypoplasia

abnormal upper incisor morphology ( J:257247 )

• only a single median maxillary central incisor (SMMCI) is present at E12.5 and E17.5, whereas two maxillary incisor teeth are present in the craniofacial midline of wild-type controls

small mandible ( J:257247 )

• at E17.5, the mandible is slightly smaller but otherwise normal

abnormal maxilla morphology ( J:257247 )

• narrowing of the anterior maxillary incisor region at E12.5

maxillary shelf hypoplasia ( J:257247 )

• the palatal processes of the maxilla are hypoplastic

abnormal premaxilla morphology ( J:257247 )

• the body of the premaxilla exhibits a variable circular midline defect while the palatal shelves of the premaxilla are hypoplastic

maxillary retrognathia ( J:257247 )

• obvious retrusion in the maxillary region at E17.5

absent palatine bone horizontal plate ( J:257247 )

• in many cases, the palatine bone lacks palatal processes, exposing the underlying presphenoid bone

palatine bone hypoplasia ( J:257247 )

• the body of the palatine bone is hypoplastic

vomer bone hypoplasia ( J:257247 )

• the vomer is hypoplastic at E17.5

abnormal vomeronasal cartilage morphology ( J:257247 )

• the paraseptal cartilages are hypoplastic at E17.5

Genotype
MGI:7387091

cx3

• Allelic Composition: Gas1^tm1Fan/Gas1^tm1Fan; Vax1^tm1Pgr/Vax1^tm1Pgr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

craniofacial

absent upper incisors ( J:257247 )

• at E15.5, double homozygotes show a complete absence of maxillary incisors, unlike single homozygotes which exhibit a single median maxillary central incisor (SMMCI)

• however, normal bilateral external nares and an intact upper lip are present, and no cleft palate is observed

growth/size/body

absent upper incisors ( J:257247 )

• at E15.5, double homozygotes show a complete absence of maxillary incisors, unlike single homozygotes which exhibit a single median maxillary central incisor (SMMCI)

• however, normal bilateral external nares and an intact upper lip are present, and no cleft palate is observed

skeleton

absent upper incisors ( J:257247 )

• at E15.5, double homozygotes show a complete absence of maxillary incisors, unlike single homozygotes which exhibit a single median maxillary central incisor (SMMCI)

• however, normal bilateral external nares and an intact upper lip are present, and no cleft palate is observed