Phenotypes associated with this allele

• Allele Symbol: Hand1^tm3Abfi
• Allele Name: targeted mutation 3, Anthony B Firulli
• Allele ID: MGI:5604130
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Hand1^tm2Eno/Hand1^tm3Abfi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S6/SvEvTac * C3H * C57BL/6	MGI:5604132
cn2	Hand1^tm3Abfi/Hand1^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6	MGI:5604134
cn3	Hand1^tm3Abfi/Hand1^+ Tg(Mpz-cre)94Imeg/0	Not Specified	MGI:5604136

Genotype
MGI:5604132

cn1

• Allelic Composition: Hand1^tm2Eno/Hand1^tm3Abfi; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6

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

mortality/aging

neonatal lethality ( J:214092 )

craniofacial

basisphenoid bone hypoplasia ( J:214092 )

nasal bone hypoplasia ( J:214092 )

• nasal bone is present but hypoplastic

abnormal craniofacial development ( J:214092 )

• distances between the lateral nasal prominences and the olfactory pits are extended at E10.5 and E11.5

• however craniofacial defects are less severe than in single conditional Hand1^tm3Abfi heterozygotes; the squamosal, jugal, and tympanic ringbones appear normal, as does the premaxilla and the mandible, there is improvement in the pterygoid bones, the size of the lamina obturans and sqamosal bones are improved, and sagittal sutures appear normal

abnormal maxillary prominence morphology ( J:214092 )

• maxillary processes are symmetrically reduced in size

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

abnormal secondary palate development ( J:214092 )

• near complete loss of the secondary palate at E18.5

abnormal palatal shelf fusion at midline ( J:214092 )

• palatal shelves fail to fuse

abnormal pharyngeal arch morphology ( J:214092 )

• E9.5 embryos exhibit increased cell death within the pharyngeal arch mesenchyme compared to controls, however level of cell death is decreased compared to the single conditional Hand1^tm3Abfi heterozygotes

abnormal tongue position ( J:214092 )

• tongue fails to drop at E14.5 at the time that palatal shelves fail to fuse

absent nasal septum ( J:214092 )

• at E14.5

midline facial cleft ( J:214092 )

• 100% penetrance of mid-face clefts, which are obvious at E12.5

• the trabecular basal pate is better developed, although there is still a cleft between the palatal processes of the palatine and maxilla bones and between the two halves of the premaxilla

digestive/alimentary system

abnormal secondary palate development ( J:214092 )

• near complete loss of the secondary palate at E18.5

abnormal palatal shelf fusion at midline ( J:214092 )

• palatal shelves fail to fuse

abnormal tongue position ( J:214092 )

• tongue fails to drop at E14.5 at the time that palatal shelves fail to fuse

embryo

abnormal pharyngeal arch morphology ( J:214092 )

• E9.5 embryos exhibit increased cell death within the pharyngeal arch mesenchyme compared to controls, however level of cell death is decreased compared to the single conditional Hand1^tm3Abfi heterozygotes

growth/size/body

nasal bone hypoplasia ( J:214092 )

• nasal bone is present but hypoplastic

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

abnormal secondary palate development ( J:214092 )

• near complete loss of the secondary palate at E18.5

abnormal palatal shelf fusion at midline ( J:214092 )

• palatal shelves fail to fuse

abnormal tongue position ( J:214092 )

• tongue fails to drop at E14.5 at the time that palatal shelves fail to fuse

absent nasal septum ( J:214092 )

• at E14.5

midline facial cleft ( J:214092 )

• 100% penetrance of mid-face clefts, which are obvious at E12.5

• the trabecular basal pate is better developed, although there is still a cleft between the palatal processes of the palatine and maxilla bones and between the two halves of the premaxilla

respiratory system

nasal bone hypoplasia ( J:214092 )

• nasal bone is present but hypoplastic

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

absent nasal septum ( J:214092 )

• at E14.5

skeleton

basisphenoid bone hypoplasia ( J:214092 )

nasal bone hypoplasia ( J:214092 )

• nasal bone is present but hypoplastic

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

Genotype
MGI:5604134

cn2

• Allelic Composition: Hand1^tm3Abfi/Hand1⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

neonatal lethality ( J:214092 )

craniofacial

abnormal sagittal suture morphology ( J:214092 )

• both sagittal sutures are aberrantly fused

abnormal basicranium morphology ( J:214092 )

• skull base defects

basisphenoid bone hypoplasia ( J:214092 )

• severely underdeveloped

short Meckel's cartilage ( J:214092 )

• Meckels cartilage (mandibular arch) is truncated at its origin with the malleus

frontal bone hypoplasia ( J:214092 )

• frontal bones are hypoplastic leading to a large gap between the frontal bones

interparietal bone hypoplasia ( J:214092 )

abnormal alisphenoid bone morphology ( J:214092 )

• lamina obturans (the bony portion of the future alisphenoid that abuts the squamosal bone) is missing

pterygoid bone hypoplasia ( J:214092 )

• severely underdeveloped

absent temporal bone squamous part ( J:214092 )

mandible hypoplasia ( J:214092 )

• proximal mandible is hypoplastic, with the two halves failing to meet at the midline

abnormal maxilla morphology ( J:214092 )

• a portion of the maxilla closest to the frontal bone is missing

short premaxilla ( J:214092 )

absent nasal bone ( J:214092 )

zygomatic bone hypoplasia ( J:214092 )

• the jugal bone, the middle bone of the zygomatic arch is hypoplastic

abnormal Reichert's cartilage morphology ( J:214092 )

• the cartilage anlage of the hyoid bone (second arch) is poorly ossified and deformed at the midline

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

abnormal secondary palate development ( J:214092 )

• near complete loss of the secondary palate at E18.5

abnormal palatal shelf fusion at midline ( J:214092 )

• palatal shelves are not fused, resulting in aberrant communication between the nasopharynx and oral cavity

abnormal pharyngeal arch morphology ( J:214092 )

• E9.5 embryos exhibit a reduction in the developmental dorso-lateral cell death domains while showing an increase in pharyngeal arch cell death

abnormal tongue position ( J:214092 )

• tongue fails to drop at E14.5 at the time that palatal shelves fail to fuse

absent nasal septum ( J:214092 )

midline facial cleft ( J:214092 )

• failure of the palatine bones and the palatal processes of the maxilla to fuse

• however, the malleus and incus (mandibular arch) and the stapes appear normal at E17

digestive/alimentary system

abnormal secondary palate development ( J:214092 )

• near complete loss of the secondary palate at E18.5

abnormal palatal shelf fusion at midline ( J:214092 )

• palatal shelves are not fused, resulting in aberrant communication between the nasopharynx and oral cavity

abnormal tongue position ( J:214092 )

• tongue fails to drop at E14.5 at the time that palatal shelves fail to fuse

embryo

abnormal pharyngeal arch morphology ( J:214092 )

• E9.5 embryos exhibit a reduction in the developmental dorso-lateral cell death domains while showing an increase in pharyngeal arch cell death

growth/size/body

absent nasal bone ( J:214092 )

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

abnormal secondary palate development ( J:214092 )

• near complete loss of the secondary palate at E18.5

abnormal palatal shelf fusion at midline ( J:214092 )

• palatal shelves are not fused, resulting in aberrant communication between the nasopharynx and oral cavity

abnormal tongue position ( J:214092 )

• tongue fails to drop at E14.5 at the time that palatal shelves fail to fuse

absent nasal septum ( J:214092 )

midline facial cleft ( J:214092 )

• failure of the palatine bones and the palatal processes of the maxilla to fuse

• however, the malleus and incus (mandibular arch) and the stapes appear normal at E17

respiratory system

absent nasal bone ( J:214092 )

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

absent nasal septum ( J:214092 )

skeleton

abnormal sagittal suture morphology ( J:214092 )

• both sagittal sutures are aberrantly fused

abnormal basicranium morphology ( J:214092 )

• skull base defects

basisphenoid bone hypoplasia ( J:214092 )

• severely underdeveloped

short Meckel's cartilage ( J:214092 )

• Meckels cartilage (mandibular arch) is truncated at its origin with the malleus

frontal bone hypoplasia ( J:214092 )

• frontal bones are hypoplastic leading to a large gap between the frontal bones

interparietal bone hypoplasia ( J:214092 )

abnormal alisphenoid bone morphology ( J:214092 )

• lamina obturans (the bony portion of the future alisphenoid that abuts the squamosal bone) is missing

pterygoid bone hypoplasia ( J:214092 )

• severely underdeveloped

absent temporal bone squamous part ( J:214092 )

mandible hypoplasia ( J:214092 )

• proximal mandible is hypoplastic, with the two halves failing to meet at the midline

abnormal maxilla morphology ( J:214092 )

• a portion of the maxilla closest to the frontal bone is missing

short premaxilla ( J:214092 )

absent nasal bone ( J:214092 )

zygomatic bone hypoplasia ( J:214092 )

• the jugal bone, the middle bone of the zygomatic arch is hypoplastic

abnormal Reichert's cartilage morphology ( J:214092 )

• the cartilage anlage of the hyoid bone (second arch) is poorly ossified and deformed at the midline

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

Genotype
MGI:5604136

cn3

• Allelic Composition: Hand1^tm3Abfi/Hand1⁺; Tg(Mpz-cre)94Imeg/0
• Genetic Background: Not Specified

craniofacial

small frontal bone ( J:214092 )

• reduced size of frontal bones at E18.5, leading to a gap between the left and right frontal bones

small nasal bone ( J:214092 )

• reduced size of nasal bones at E18.5

abnormal nasal capsule morphology ( J:214092 )

• fusion of the nasal capsule is nearly complete at E18.5 although not phenotypically normal

abnormal palate development ( J:214092 )

• palate formation is improved compared to heterozygous Hand1^tm3Abfi Tg(Wnt1-cre)2Sor mice

digestive/alimentary system

abnormal palate development ( J:214092 )

• palate formation is improved compared to heterozygous Hand1^tm3Abfi Tg(Wnt1-cre)2Sor mice

growth/size/body

small nasal bone ( J:214092 )

• reduced size of nasal bones at E18.5

abnormal nasal capsule morphology ( J:214092 )

• fusion of the nasal capsule is nearly complete at E18.5 although not phenotypically normal

abnormal palate development ( J:214092 )

• palate formation is improved compared to heterozygous Hand1^tm3Abfi Tg(Wnt1-cre)2Sor mice

respiratory system

small nasal bone ( J:214092 )

• reduced size of nasal bones at E18.5

abnormal nasal capsule morphology ( J:214092 )

• fusion of the nasal capsule is nearly complete at E18.5 although not phenotypically normal

skeleton

small frontal bone ( J:214092 )

• reduced size of frontal bones at E18.5, leading to a gap between the left and right frontal bones

small nasal bone ( J:214092 )

• reduced size of nasal bones at E18.5

abnormal nasal capsule morphology ( J:214092 )

• fusion of the nasal capsule is nearly complete at E18.5 although not phenotypically normal