Phenotypes associated with this allele

• Allele Symbol: E2f1^{Tg(Wnt1-cre)2Sor}
• Allele Name: transgene insertion 2, Philippe Soriano
• Allele ID: MGI:5485027
• Summary: 32 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Abcc6^tm1c(EUCOMM)Wtsi/Abcc6^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/?	B6.Cg-E2f1^Tg(Wnt1-cre)2Sor Abcc6^tm1c(EUCOMM)Wtsi	MGI:6241498
cn2	Abcc6^tm1c(EUCOMM)Wtsi/Abcc6^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/? Speer6-ps1^Tg(Alb-cre)21Mgn/?	B6.Cg-E2f1^Tg(Wnt1-cre)2Sor Abcc6^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn	MGI:6241501
cn3	Cfdp1^tm1Dkwpd/Cfdp1^tm2.1Dkwpd E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129 * 129S2/SvPas * C3H * C57BL/6	MGI:7711575
cn4	Anp32e^tm1Mak/Anp32e^tm1Mak Cfdp1^tm1Dkwpd/Cfdp1^tm2.1Dkwpd E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129 * C3H * C57BL/6	MGI:7711577
cn5	Chd7^tm2a(EUCOMM)Wtsi/Chd7^tm2a(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+ Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+	involves: 129 * C3H * C57BL/6 * C57BL/6N	MGI:6490654
cn6	E2f1^Tg(Wnt1-cre)2Sor/E2f1^+ Snrpb^em1Lajm/Snrpb^+ Trp53^tm1Brn/Trp53^+	involves: 129P2/OlaHsd * C3H * C57BL/6 * CD1	MGI:7438238
cn7	E2f1^Tg(Wnt1-cre)2Sor/E2f1^+ Snrpb^em1Lajm/Snrpb^+ Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * C3H * C57BL/6 * CD1	MGI:7438244
cn8	Thap11^tm1Tpz/Thap11^tm1Tpz E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C3H * C57BL/6	MGI:6861816
cn9	Thap11^tm1Tpz/Thap11^em1Poche E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J	MGI:7310234
cn10	Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J	MGI:7341522
cn11	Tg(ACTB-Edn1)1398Clou/0 E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C3H * C57BL/6	MGI:5754726
cn12	Tg(ACTB-Edn1)1408Clou/0 E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C3H * C57BL/6	MGI:5754728
cn13	Tg(ACTB-Edn1)721Clou/0 E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C3H * C57BL/6	MGI:5754723
cn14	Tg(ACTB-Edn1)1416Clou/0 E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C3H * C57BL/6	MGI:5754729
cn15	Mmachc^em1Poche/Mmachc^em1Poche E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6J	MGI:7310233
cn16	Kctd15^tm1c(EUCOMM)Wtsi/Kctd15^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7657812
cn17	Kctd1^tm1c(EUCOMM)Wtsi/Kctd1^+ Kctd15^tm1c(EUCOMM)Wtsi/Kctd15^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7657816
cn18	Kctd1^tm1c(EUCOMM)Wtsi/Kctd1^tm1c(EUCOMM)Wtsi Kctd15^tm1c(EUCOMM)Wtsi/Kctd15^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7657817
cn19	Kctd1^tm1c(EUCOMM)Wtsi/Kctd1^tm1c(EUCOMM)Wtsi Kctd15^tm1c(EUCOMM)Wtsi/Kctd15^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7657819
cn20	Kctd1^tm1c(EUCOMM)Wtsi/Kctd1^+ Kctd15^tm1c(EUCOMM)Wtsi/Kctd15^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7657818
cn21	Hand1^tm2Eno/Hand1^tm3Abfi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S6/SvEvTac * C3H * C57BL/6	MGI:5604132
cn22	Hand1^tm2Eno/Hand1^tm4Abfi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S6/SvEvTac * C3H * C57BL/6	MGI:5604133
cn23	Sox9^tm2Crm/Sox9^+ Rr80^em1Jwsk/Rr80^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S7/SvEvBrd * C3H * C57BL/6J * FVB/NJ	MGI:6720292
cn24	Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk E2f1^Tg(Wnt1-cre)2Sor/E2f1^+ Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+	involves: 129S/Sv * 129X1/SvJ * C57BL/6J	MGI:7341534
cn25	Vegfa^tm2Gne/Vegfa^tm2Gne E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129/Sv * C3H * C57BL/6	MGI:7343722
cn26	Hand1^tm3Abfi/Hand1^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6	MGI:5604134
cn27	Hand1^tm4Abfi/Hand1^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6	MGI:5604135
cn28	C2cd3^em2Brgm/C2cd3^em2Brgm E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6	MGI:6887946
cn29	C2cd3^tm1c(EUCOMM)Wtsi/C2cd3^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6	MGI:6887948
cn30	E2f1^Tg(Wnt1-cre)2Sor/E2f1^+ Snrpb^em1Lajm/Snrpb^+	involves: C3H * C57BL/6 * C57BL/6J * CD1	MGI:7437965
cn31	Ankrd11^tm1c(EUCOMM)Wtsi/Ankrd11^tm1c(EUCOMM)Wtsi E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6 * C57BL/6N	MGI:6885557
cn32	Ankrd11^tm1c(EUCOMM)Wtsi/Ankrd11^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: C3H * C57BL/6 * C57BL/6N	MGI:7336829

Genotype
MGI:6241498

cn1

• Allelic Composition: Abcc6^{tm1c(EUCOMM)Wtsi}/Abcc6^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/?
• Genetic Background: B6.Cg-E2f1^{Tg(Wnt1-cre)2Sor} Abcc6^{tm1c(EUCOMM)Wtsi}

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

homeostasis/metabolism

calcinosis ( J:252837 )

integument

abnormal snout skin morphology ( J:252837 )

calcified skin ( J:252837 )

• 1 out of 22 mice exhibit mild calcification of the fibrous capsule surrounding the muzzle vibrissae occurs at 20 weeks of age

• at one year of age, the calcification phenotype shows reduced penetrance and variable expression

growth/size/body

abnormal snout skin morphology ( J:252837 )

craniofacial

abnormal snout skin morphology ( J:252837 )

Genotype
MGI:6241501

cn2

• Allelic Composition: Abcc6^{tm1c(EUCOMM)Wtsi}/Abcc6^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/?; Speer6-ps1^{Tg(Alb-cre)21Mgn}/?
• Genetic Background: B6.Cg-E2f1^{Tg(Wnt1-cre)2Sor} Abcc6^{tm1c(EUCOMM)Wtsi} Speer6-ps1^{Tg(Alb-cre)21Mgn}

homeostasis/metabolism

calcinosis ( J:252837 )

integument

abnormal snout skin morphology ( J:252837 )

calcified skin ( J:252837 )

• 5 out of 13 mice exhibit calcification of the fibrous capsule surrounding the muzzle vibrissae occurs at 20 weeks of age

growth/size/body

abnormal snout skin morphology ( J:252837 )

craniofacial

abnormal snout skin morphology ( J:252837 )

Genotype
MGI:7711575

cn3

• Allelic Composition: Cfdp1^tm1Dkwpd/Cfdp1^tm2.1Dkwpd; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129 * 129S2/SvPas * C3H * C57BL/6

craniofacial

abnormal craniofacial morphology ( J:349245 )

• extensive craniofacial abnormalities in the mid face region, nose, maxillary region, mandibular region, and flattened forebrain region at E16

abnormal incisor morphology ( J:349245 )

• underdeveloped with altered morphology at E16

small mandible ( J:349245 )

• small and rudimentary at E16

• consists mainly of soft tissue lacking mineralized bone at E16

short mandible ( J:349245 )

abnormal maxilla morphology ( J:349245 )

• at E16

flat head ( J:349245 )

• flattened forebrain region at E16

cellular

abnormal intracellular organelle physiology ( J:349245 )

• H2A.Z and RCC1 levels at the major satellite repeats are significantly decreased

growth/size/body

abnormal incisor morphology ( J:349245 )

• underdeveloped with altered morphology at E16

flat head ( J:349245 )

• flattened forebrain region at E16

skeleton

abnormal incisor morphology ( J:349245 )

• underdeveloped with altered morphology at E16

small mandible ( J:349245 )

• small and rudimentary at E16

• consists mainly of soft tissue lacking mineralized bone at E16

short mandible ( J:349245 )

abnormal maxilla morphology ( J:349245 )

• at E16

abnormal intramembranous bone ossification ( J:349245 )

• consists mainly of soft tissue lacking mineralized bone at E16

Genotype
MGI:7711577

cn4

• Allelic Composition: Anp32e^tm1Mak/Anp32e^tm1Mak; Cfdp1^tm1Dkwpd/Cfdp1^tm2.1Dkwpd; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129 * C3H * C57BL/6

cellular

abnormal intracellular organelle physiology ( J:349245 )

N • H2A.Z and RCC1 levels at the major satellite repeats are increased in rescue mice relative to both conditional mutant mice wild-type for Anp32e and wild-type controls

craniofacial

craniofacial phenotype ( J:349245 )

N • loss of Anp32e expression largely rescues the craniofacial phenotype seen in conditional mutant mice wild-type for Anp32e

N • maxilla and mandible are mineralized unlike in conditional mutant mice wild-type for Anp32e

Genotype
MGI:6490654

cn5

• Allelic Composition: Chd7^{tm2a(EUCOMM)Wtsi}/Chd7^{tm2a(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129 * C3H * C57BL/6 * C57BL/6N

mortality/aging

perinatal lethality, complete penetrance ( J:298597 )

cardiovascular system

pulmonary trunk hypoplasia ( J:298597 )

• about 5% of mutants show a hypoplastic pulmonary trunk at E15.5 and E16.5

interrupted aortic arch, type b ( J:298597 )

• about 30% of mutants exhibit interrupted aortic arch, type b at E15.5 and E16.5

abnormal conotruncal ridge morphology ( J:298597 )

• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5

double outlet right ventricle ( J:298597 )

• all mutants exhibit the double outlet right ventricle at E15.5 and E16.5

ventricular septal defect ( J:298597 )

• all mutants exhibit a ventricular septal defect at E15.5 and E16.5

craniofacial

small frontal bone ( J:298597 )

• E17.5 mutants show a smaller frontal bone

small mandible ( J:298597 )

• E17.5 mutants exhibit a smaller mandible

small maxilla ( J:298597 )

• E17.5 mutants exhibit a smaller maxilla

abnormal pharyngeal arch morphology ( J:298597 )

• 30% of mutants show increased cell death in the pharyngeal arch region

• however, no reduction in cell proliferation is seen in the pharyngeal arch regions at E11.5

embryo

abnormal pharyngeal arch morphology ( J:298597 )

• 30% of mutants show increased cell death in the pharyngeal arch region

• however, no reduction in cell proliferation is seen in the pharyngeal arch regions at E11.5

impaired cranial neural crest cell differentiation ( J:298597 )

• marker analysis at E11.5 indicates that differentiation of cranial neural crest cells into smooth muscle cells is reduced

abnormal embryonic tissue physiology ( J:298597 )

• cell proliferation in the neural crest cell derivatives, aorta and pulmonary trunk walls, is reduced at E12.5

• 30% of mutants show increased cell death in the pharyngeal arch region

• however, no reduction in cell proliferation is seen in the dorsal neural tube, pharyngeal arch regions and outflow tract cushions at E11.5 and no increase in cell death is seen in the dorsal neural tube and outflow tract cushions at E11.5

abnormal cranial neural crest cell migration ( J:298597 )

• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5 however, no increase in cell death or reduction in cell proliferation is seen in the outflow tract cushions, indicating that cranial neural crest cell migration to outflow tract cushions is reduced

nervous system

impaired cranial neural crest cell differentiation ( J:298597 )

• marker analysis at E11.5 indicates that differentiation of cranial neural crest cells into smooth muscle cells is reduced

skeleton

small frontal bone ( J:298597 )

• E17.5 mutants show a smaller frontal bone

small mandible ( J:298597 )

• E17.5 mutants exhibit a smaller mandible

small maxilla ( J:298597 )

• E17.5 mutants exhibit a smaller maxilla

cellular

abnormal cranial neural crest cell migration ( J:298597 )

• the number of neural crest cells in the proximal outflow tract cushions is reduced at E11.5 however, no increase in cell death or reduction in cell proliferation is seen in the outflow tract cushions, indicating that cranial neural crest cell migration to outflow tract cushions is reduced

Genotype
MGI:7438238

cn6

• Allelic Composition: E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺; Snrpb^em1Lajm/Snrpb⁺; Trp53^tm1Brn/Trp53⁺
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * CD1

craniofacial

abnormal craniofacial morphology ( J:326544 )

• no reduction in craniofacial defects in conditional double mutant embryos at E10.5 and E17.5 compared to mutant embryos with wild-type levels of Trp53

Genotype
MGI:7438244

cn7

• Allelic Composition: E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺; Snrpb^em1Lajm/Snrpb⁺; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6 * CD1

mortality/aging

perinatal lethality, complete penetrance ( J:326544 )

• pups born alive die between P1 and P2

• however, most pups do survive to birth unlike in mutant mice wild-type for Trp53

craniofacial

abnormal mandible morphology ( J:326544 )

• asymmetric and abnormal development of the lower jaw

micrognathia ( J:326544 )

• at E18.5

cleft palate ( J:326544 )

short snout ( J:326544 )

• at E18.5

skeleton

abnormal mandible morphology ( J:326544 )

• asymmetric and abnormal development of the lower jaw

micrognathia ( J:326544 )

• at E18.5

abnormal bone ossification ( J:326544 )

• reduced ossification of the frontal bone

growth/size/body

cleft palate ( J:326544 )

short snout ( J:326544 )

• at E18.5

microcephaly ( J:326544 )

• at E18.5

digestive/alimentary system

cleft palate ( J:326544 )

Genotype
MGI:6861816

cn8

• Allelic Composition: Thap11^tm1Tpz/Thap11^tm1Tpz; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C3H * C57BL/6

craniofacial

abnormal craniofacial development ( J:317822 )

• mice show almost complete agenesis of the neural crest-derived craniofacial skeleton

Genotype
MGI:7310234

cn9

• Allelic Composition: Thap11^tm1Tpz/Thap11^em1Poche; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J

integument

belly spot ( J:317822 )

• 2 out of 5 mice exhibit white belly spots

decreased digit pigmentation ( J:317822 )

• hypopigmented paws

limbs/digits/tail

decreased digit pigmentation ( J:317822 )

• hypopigmented paws

pigmentation

belly spot ( J:317822 )

• 2 out of 5 mice exhibit white belly spots

decreased digit pigmentation ( J:317822 )

• hypopigmented paws

Genotype
MGI:7341522

cn10

• Allelic Composition: Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6J

mortality/aging

neonatal lethality, complete penetrance ( J:279139 )

• mice are born at the expected Mendelian ratio but die at P1

craniofacial

abnormal craniofacial bone morphology ( J:279139 )

• severe hypoplasia and reduced ossification of many neural crest-derived bones at E18.5

• both the shape and size of most neural crest-derived bones including alisphenoid, premaxilla, palatal process of premaxilla, palatal process of maxilla and palatine are affected

abnormal frontal bone morphology ( J:279139 )

• frontal bones are hypoplastic and widely separated leaving a wide dorsal opening

frontal bone hypoplasia ( J:279139 )

small mandible ( J:279139 )

abnormal nasal bone morphology ( J:279139 )

• reduced ossification of the nasal bone at E18.5

absent palatine bone horizontal plate ( J:279139 )

• palatal process of palatine bone is missing at E18.5

abnormal palatal mesenchymal cell proliferation ( J:279139 )

• Ki67 immunohistochemistry showed a significant decrease in mesenchymal cell proliferation in middle palatal shelves sections at E15.5

palatal shelves fail to meet at midline ( J:279139 )

• palatal shelves are elevated above the tongue to a horizontal position but completely fail to fuse at the midline throughout the anterior-posterior axis

cleft secondary palate ( J:279139 )

• all fetuses show a secondary cleft palate defect at E15.5 and E18.5

skeleton

skeleton phenotype ( J:279139 )

N • no apparent defects in the axial skeleton at E18.5

abnormal craniofacial bone morphology ( J:279139 )

• severe hypoplasia and reduced ossification of many neural crest-derived bones at E18.5

• both the shape and size of most neural crest-derived bones including alisphenoid, premaxilla, palatal process of premaxilla, palatal process of maxilla and palatine are affected

abnormal frontal bone morphology ( J:279139 )

• frontal bones are hypoplastic and widely separated leaving a wide dorsal opening

frontal bone hypoplasia ( J:279139 )

small mandible ( J:279139 )

abnormal nasal bone morphology ( J:279139 )

• reduced ossification of the nasal bone at E18.5

absent palatine bone horizontal plate ( J:279139 )

• palatal process of palatine bone is missing at E18.5

decreased bone ossification ( J:279139 )

• reduced ossification of the nasal bone and many neural crest-derived bones at E18.5

growth/size/body

abnormal nasal bone morphology ( J:279139 )

• reduced ossification of the nasal bone at E18.5

absent palatine bone horizontal plate ( J:279139 )

• palatal process of palatine bone is missing at E18.5

abnormal palatal mesenchymal cell proliferation ( J:279139 )

• Ki67 immunohistochemistry showed a significant decrease in mesenchymal cell proliferation in middle palatal shelves sections at E15.5

palatal shelves fail to meet at midline ( J:279139 )

• palatal shelves are elevated above the tongue to a horizontal position but completely fail to fuse at the midline throughout the anterior-posterior axis

cleft secondary palate ( J:279139 )

• all fetuses show a secondary cleft palate defect at E15.5 and E18.5

digestive/alimentary system

absent palatine bone horizontal plate ( J:279139 )

• palatal process of palatine bone is missing at E18.5

abnormal palatal mesenchymal cell proliferation ( J:279139 )

• Ki67 immunohistochemistry showed a significant decrease in mesenchymal cell proliferation in middle palatal shelves sections at E15.5

palatal shelves fail to meet at midline ( J:279139 )

• palatal shelves are elevated above the tongue to a horizontal position but completely fail to fuse at the midline throughout the anterior-posterior axis

cleft secondary palate ( J:279139 )

• all fetuses show a secondary cleft palate defect at E15.5 and E18.5

cardiovascular system

cardiovascular system phenotype ( J:279139 )

N • no alterations in smooth muscle actin staining in the aortic arches and normal septation and alignment of the aorta and pulmonary trunk at E17.5, indicating normal cardiac outflow tract development

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:279139 )

N • normal thymus and adrenal gland (chromaffin cells) morphology at E17.5

respiratory system

abnormal nasal bone morphology ( J:279139 )

• reduced ossification of the nasal bone at E18.5

Genotype
MGI:5754726

cn11

• Allelic Composition: Tg(ACTB-Edn1)1398Clou/0; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6

craniofacial

temporal bone squamous part hypoplasia ( J:221133 )

• hypoplastic squamosal bone

abnormal mandibular angle morphology ( J:221133 )

• duplication of the angular process

absent mandibular coronoid process ( J:221133 )

• the coronoid process of the mandible is lost due to fusion of the mandible and the duplicated mandible

upper jaw to lower jaw transformation ( J:221133 )

• complete homeotic transformation of the upper jaw (maxilla and jugal bones) into a mandible-like structure, with duplicated angular and condylar processes

palatine bone hypoplasia ( J:221133 )

abnormal zygomatic bone morphology ( J:221133 )

• complete homeotic transformation of the upper jaw (maxilla and jugal bones) into a mandible-like structure, with duplicated angular and condylar processes

ectopic cranial bone ( J:221133 )

• an ectopic bone is present suggestive of duplicated gonial bone and/or part of the tympanic ring

abnormal incus morphology ( J:221133 )

• additional cartilage is present that appears to be duplication of the malleus and incus

abnormal malleus morphology ( J:221133 )

• additional cartilage is present that appears to be duplication of the malleus and incus

gonial bone hypoplasia ( J:221133 )

cleft palate ( J:221133 )

digestive/alimentary system

palatine bone hypoplasia ( J:221133 )

cleft palate ( J:221133 )

growth/size/body

palatine bone hypoplasia ( J:221133 )

cleft palate ( J:221133 )

hearing/vestibular/ear

abnormal incus morphology ( J:221133 )

• additional cartilage is present that appears to be duplication of the malleus and incus

abnormal malleus morphology ( J:221133 )

• additional cartilage is present that appears to be duplication of the malleus and incus

gonial bone hypoplasia ( J:221133 )

tympanic ring hypoplasia ( J:221133 )

• hypoplastic tympanic ring

skeleton

temporal bone squamous part hypoplasia ( J:221133 )

• hypoplastic squamosal bone

abnormal mandibular angle morphology ( J:221133 )

• duplication of the angular process

absent mandibular coronoid process ( J:221133 )

• the coronoid process of the mandible is lost due to fusion of the mandible and the duplicated mandible

upper jaw to lower jaw transformation ( J:221133 )

• complete homeotic transformation of the upper jaw (maxilla and jugal bones) into a mandible-like structure, with duplicated angular and condylar processes

palatine bone hypoplasia ( J:221133 )

abnormal zygomatic bone morphology ( J:221133 )

• complete homeotic transformation of the upper jaw (maxilla and jugal bones) into a mandible-like structure, with duplicated angular and condylar processes

ectopic cranial bone ( J:221133 )

• an ectopic bone is present suggestive of duplicated gonial bone and/or part of the tympanic ring

abnormal incus morphology ( J:221133 )

• additional cartilage is present that appears to be duplication of the malleus and incus

abnormal malleus morphology ( J:221133 )

• additional cartilage is present that appears to be duplication of the malleus and incus

gonial bone hypoplasia ( J:221133 )

Genotype
MGI:5754728

cn12

• Allelic Composition: Tg(ACTB-Edn1)1408Clou/0; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6

craniofacial

craniofacial phenotype ( J:221133 )

N • mice do not exhibit craniofacial malformations

Genotype
MGI:5754723

cn13

• Allelic Composition: Tg(ACTB-Edn1)721Clou/0; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6

craniofacial

basisphenoid bone hypoplasia ( J:221133 )

• basisphenoid bone is hypoplastic in the duplicated mandible

abnormal Meckel's cartilage morphology ( J:221133 )

• duplication of Meckel's cartilage in the duplicated mandible

abnormal temporal bone squamous part morphology ( J:221133 )

• the squamosal bone is deformed in the duplicated mandible

abnormal mandible morphology ( J:221133 )

• the duplicated mandible contains a duplicated Meckels cartilage, absent jugal and palatine bones, deformed squamosal bones, a hypoplastic basisphenoid bone and a palatal cleft

upper jaw to lower jaw transformation ( J:221133 )

• transformation of the maxilla into a mandible-like structure that is fused with the mandible

absent palatine bone ( J:221133 )

• palatine bone is absent in the duplicated mandible

absent zygomatic bone ( J:221133 )

• jugal bone is absent in the duplicated mandible

cleft palate ( J:221133 )

midline facial cleft ( J:221133 )

• mice exhibit a large mid-facial cleft

digestive/alimentary system

cleft palate ( J:221133 )

growth/size/body

cleft palate ( J:221133 )

midline facial cleft ( J:221133 )

• mice exhibit a large mid-facial cleft

skeleton

basisphenoid bone hypoplasia ( J:221133 )

• basisphenoid bone is hypoplastic in the duplicated mandible

abnormal Meckel's cartilage morphology ( J:221133 )

• duplication of Meckel's cartilage in the duplicated mandible

abnormal temporal bone squamous part morphology ( J:221133 )

• the squamosal bone is deformed in the duplicated mandible

abnormal mandible morphology ( J:221133 )

• the duplicated mandible contains a duplicated Meckels cartilage, absent jugal and palatine bones, deformed squamosal bones, a hypoplastic basisphenoid bone and a palatal cleft

upper jaw to lower jaw transformation ( J:221133 )

• transformation of the maxilla into a mandible-like structure that is fused with the mandible

absent palatine bone ( J:221133 )

• palatine bone is absent in the duplicated mandible

absent zygomatic bone ( J:221133 )

• jugal bone is absent in the duplicated mandible

Genotype
MGI:5754729

cn14

• Allelic Composition: Tg(ACTB-Edn1)1416Clou/0; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6

craniofacial

abnormal Meckel's cartilage morphology ( J:221133 )

• duplication of the Meckel's cartilage

temporal bone squamous part hypoplasia ( J:221133 )

• hypoplastic squamosal bone

abnormal mandibular angle morphology ( J:221133 )

• the condylar and angular processes are duplicated

absent mandibular coronoid process ( J:221133 )

• loss of the coronoid process

upper jaw to lower jaw transformation ( J:221133 )

• transformation of the maxilla into a mandible-like structure

palatine bone hypoplasia ( J:221133 )

malleus hypoplasia ( J:221133 )

midline facial cleft ( J:221133 )

• 70% of mutants exhibit a large mid-facial cleft; cleft does not affect the transformation of the maxilla

growth/size/body

palatine bone hypoplasia ( J:221133 )

midline facial cleft ( J:221133 )

• 70% of mutants exhibit a large mid-facial cleft; cleft does not affect the transformation of the maxilla

hearing/vestibular/ear

malleus hypoplasia ( J:221133 )

tympanic ring hypoplasia ( J:221133 )

• hypoplastic tympanic ring

skeleton

abnormal Meckel's cartilage morphology ( J:221133 )

• duplication of the Meckel's cartilage

temporal bone squamous part hypoplasia ( J:221133 )

• hypoplastic squamosal bone

abnormal mandibular angle morphology ( J:221133 )

• the condylar and angular processes are duplicated

absent mandibular coronoid process ( J:221133 )

• loss of the coronoid process

upper jaw to lower jaw transformation ( J:221133 )

• transformation of the maxilla into a mandible-like structure

palatine bone hypoplasia ( J:221133 )

malleus hypoplasia ( J:221133 )

ectopic cartilage ( J:221133 )

• the middle ear is composed of a large piece of ectopic cartilage

digestive/alimentary system

palatine bone hypoplasia ( J:221133 )

Genotype
MGI:7310233

cn15

• Allelic Composition: Mmachc^em1Poche/Mmachc^em1Poche; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6 * C57BL/6J

craniofacial

craniofacial phenotype ( J:317822 )

N • embryos show no obvious craniofacial phenotype

Genotype
MGI:7657812

cn16

• Allelic Composition: Kctd15^{tm1c(EUCOMM)Wtsi}/Kctd15^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N
• Cell Lines: EPD0177_1_E09

pigmentation

belly spot ( J:344153 )

• mice exhibit a white belly patch, a loss of pigmentation phenotype with absence of melanocytes that is pathognomonic for an NCC-derived melanoblast migration defect

integument

belly spot ( J:344153 )

• mice exhibit a white belly patch, a loss of pigmentation phenotype with absence of melanocytes that is pathognomonic for an NCC-derived melanoblast migration defect

cardiovascular system

cardiovascular system phenotype ( J:344153 )

N • mice do not exhibit any cardiac abnormalities at PO

Genotype
MGI:7657816

cn17

• Allelic Composition: Kctd1^{tm1c(EUCOMM)Wtsi}/Kctd1⁺; Kctd15^{tm1c(EUCOMM)Wtsi}/Kctd15⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N
• Cell Lines: EPD0177_1_E09

pigmentation

pigmentation phenotype ( J:344153 )

N • mice do not exhibit a pigmentation defect

integument

integument phenotype ( J:344153 )

N • newborn mice do not exhibit a thinned epidermis of the midline scalp

craniofacial

craniofacial phenotype ( J:344153 )

N • newborn mice exhibit normal incisor formation

Genotype
MGI:7657817

cn18

• Allelic Composition: Kctd1^{tm1c(EUCOMM)Wtsi}/Kctd1^{tm1c(EUCOMM)Wtsi}; Kctd15^{tm1c(EUCOMM)Wtsi}/Kctd15⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N
• Cell Lines: EPD0177_1_E09

pigmentation

belly spot ( J:344153 )

• mice exhibit smaller white belly patches than mice that are homozygous for Kctd15^{tm1c(EUCOMM)Wtsi} and heterozygous for E2f1^{Tg(Wnt1-cre)2Sor}

integument

belly spot ( J:344153 )

• mice exhibit smaller white belly patches than mice that are homozygous for Kctd15^{tm1c(EUCOMM)Wtsi} and heterozygous for E2f1^{Tg(Wnt1-cre)2Sor}

Genotype
MGI:7657819

cn19

• Allelic Composition: Kctd1^{tm1c(EUCOMM)Wtsi}/Kctd1^{tm1c(EUCOMM)Wtsi}; Kctd15^{tm1c(EUCOMM)Wtsi}/Kctd15^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N
• Cell Lines: EPD0177_1_E09

integument

thin epidermis ( J:344153 )

• newborns exhibit thin/eroded epidermis of the midline scalp

• a thinned epidermis with a flat Krt5+ basal layer overlying the interfrontal suture is noted at PO

skin lesions ( J:344153 )

• aplasia cutis congenita (ACC)-like lesions occur along abnormal interfrontal or sagittal sutures and show a thin epidermis with a flat Krt5+ basal layer

craniofacial

abnormal cranial suture morphology ( J:344153 )

• at P0, mice show abnormal, overextended midline cranial sutures with a receded osteogenic front

wide metopic suture ( J:344153 )

• at P0, mice show an increased distance between frontal bones at the site where the interfrontal suture crosses with the coronal suture

short frontal bone ( J:344153 )

• at P0, mice exhibit shortened frontal bones

absent incisors ( J:344153 )

• at P0, mice exhibit absence of mandibular and maxillary incisors

absent lower incisors ( J:344153 )

• absence of mandibular incisors at P0

absent upper incisors ( J:344153 )

• absence of maxillary incisors at P0

abnormal craniofacial development ( J:344153 )

• newborns show congenital bone/suture defects of neural crest cell (NCC)-derived structures of the midline skull associated with overlying membranous aplasia cutis congenita (ACC)-like skin defects with epidermal thinning

• midline skull/suture defects likely cause ACC as a result of reduced spatiotemporal expression of keratinocyte-promoting growth factors at that site

abnormal nose morphology ( J:344153 )

• at P0, mice exhibit nasal airway abnormalities

• flat nasal structures are noted at E17.0

absent nasal bone ( J:344153 )

• microCT images show loss of nasal bones at P0

small nasal bone ( J:344153 )

• at P0, mice exhibit diminished nasal bones

abnormal nasal cartilage morphology ( J:344153 )

• at P0, mice exhibit diminished nasal cartilage

nervous system

ectopic neuron ( J:344153 )

• at P0, mice display a cutaneous midline scalp mass consisting of heterotopic beta3-tubulin+ neuronal tissue, similar to heterotopic brain tissue observed at skin sites adjacent to membranous ACC lesions in patients

vision/eye

abnormal eyelid development ( J:344153 )

• open eyes with abnormal eyelids are noted at E17.0 and P0

eyelids open at birth ( J:344153 )

• mice have open eyelids at P0

cardiovascular system

abnormal heart morphology ( J:344153 )

• at P0, mice show cardiac defects, including subaortic membranous ventricular septal defects (VSDs), an overriding aorta, and bicuspid aortic valves

overriding aortic valve ( J:344153 )

• at PO, hearts show an overriding aorta

perimembraneous ventricular septal defect ( J:344153 )

• mice exhibit congenital subaortic membranous VSDs

bicuspid aortic valve ( J:344153 )

• at PO, hearts show bicuspid aortic valves

growth/size/body

absent incisors ( J:344153 )

• at P0, mice exhibit absence of mandibular and maxillary incisors

absent lower incisors ( J:344153 )

• absence of mandibular incisors at P0

absent upper incisors ( J:344153 )

• absence of maxillary incisors at P0

abnormal nose morphology ( J:344153 )

• at P0, mice exhibit nasal airway abnormalities

• flat nasal structures are noted at E17.0

absent nasal bone ( J:344153 )

• microCT images show loss of nasal bones at P0

small nasal bone ( J:344153 )

• at P0, mice exhibit diminished nasal bones

abnormal nasal cartilage morphology ( J:344153 )

• at P0, mice exhibit diminished nasal cartilage

abnormal scalp morphology ( J:344153 )

• newborns exhibit thin/eroded epidermis of the midline scalp; whole-mount Krt5 and ILB4 immunolabeling of scalp skin shows an aplasia cutis congenita (ACC)-like region

skeleton

abnormal cranial suture morphology ( J:344153 )

• at P0, mice show abnormal, overextended midline cranial sutures with a receded osteogenic front

wide metopic suture ( J:344153 )

• at P0, mice show an increased distance between frontal bones at the site where the interfrontal suture crosses with the coronal suture

short frontal bone ( J:344153 )

• at P0, mice exhibit shortened frontal bones

absent incisors ( J:344153 )

• at P0, mice exhibit absence of mandibular and maxillary incisors

absent lower incisors ( J:344153 )

• absence of mandibular incisors at P0

absent upper incisors ( J:344153 )

• absence of maxillary incisors at P0

absent nasal bone ( J:344153 )

• microCT images show loss of nasal bones at P0

small nasal bone ( J:344153 )

• at P0, mice exhibit diminished nasal bones

abnormal nasal cartilage morphology ( J:344153 )

• at P0, mice exhibit diminished nasal cartilage

abnormal intramembranous bone ossification ( J:344153 )

• at P0, mice show reduced ossification along the interfrontal and sagittal sutures and expanded non-ossified area at that site

delayed intramembranous bone ossification ( J:344153 )

• at P0, mice show delayed frontal bone ossification along the interfrontal suture

delayed cranial suture closure ( J:344153 )

• at P0, mice delayed ossification of the interfrontal suture

respiratory system

abnormal nose morphology ( J:344153 )

• at P0, mice exhibit nasal airway abnormalities

• flat nasal structures are noted at E17.0

absent nasal bone ( J:344153 )

• microCT images show loss of nasal bones at P0

small nasal bone ( J:344153 )

• at P0, mice exhibit diminished nasal bones

abnormal nasal cartilage morphology ( J:344153 )

• at P0, mice exhibit diminished nasal cartilage

Genotype
MGI:7657818

cn20

• Allelic Composition: Kctd1^{tm1c(EUCOMM)Wtsi}/Kctd1⁺; Kctd15^{tm1c(EUCOMM)Wtsi}/Kctd15^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N
• Cell Lines: EPD0177_1_E09

integument

belly spot ( J:344153 )

• mice exhibit larger white belly patches than mice that are homozygous for Kctd15^{tm1c(EUCOMM)Wtsi} and heterozygous for E2f1^{Tg(Wnt1-cre)2Sor}

pigmentation

belly spot ( J:344153 )

• mice exhibit larger white belly patches than mice that are homozygous for Kctd15^{tm1c(EUCOMM)Wtsi} and heterozygous for E2f1^{Tg(Wnt1-cre)2Sor}

Genotype
MGI:5604132

cn21

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

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:5604133

cn22

• Allelic Composition: Hand1^tm2Eno/Hand1^tm4Abfi; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6

mortality/aging

neonatal lethality ( J:214092 )

craniofacial

temporal bone squamous part hypoplasia ( J:214092 )

• squamosal bone is slightly hypoplastic

mandible hypoplasia ( J:214092 )

• proximal mandible is slightly hypoplastic

decreased maxillary shelf size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

decreased palatine bone horizontal plate size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

absent middle ear ossicles ( J:214092 )

• the middle-ear ossicles are either hypoplastic or absent

middle ear ossicle hypoplasia ( J:214092 )

• the middle-ear ossicles are either hypoplastic or absent, although portions of the alisphenoid appear better developed

abnormal craniofacial development ( J:214092 )

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

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 )

• mixed penetrance of palatal shelf fusion, although clefting is fully penetrant

abnormal pharyngeal arch morphology ( J:214092 )

• E9.5 embryos exhibit decreased cell death within the pharyngeal arch mesenchyme compared to single conditional Hand1^tm4Abfi heterozygotes

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

digestive/alimentary system

decreased maxillary shelf size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

decreased palatine bone horizontal plate size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

abnormal secondary palate development ( J:214092 )

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

abnormal palatal shelf fusion at midline ( J:214092 )

• mixed penetrance of palatal shelf fusion, although clefting is fully penetrant

embryo

abnormal pharyngeal arch morphology ( J:214092 )

• E9.5 embryos exhibit decreased cell death within the pharyngeal arch mesenchyme compared to single conditional Hand1^tm4Abfi heterozygotes

growth/size/body

decreased maxillary shelf size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

decreased palatine bone horizontal plate size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

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 )

• mixed penetrance of palatal shelf fusion, although clefting is fully penetrant

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

hearing/vestibular/ear

absent middle ear ossicles ( J:214092 )

• the middle-ear ossicles are either hypoplastic or absent

middle ear ossicle hypoplasia ( J:214092 )

• the middle-ear ossicles are either hypoplastic or absent, although portions of the alisphenoid appear better developed

respiratory system

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

absent nasal septum ( J:214092 )

• at E14.5

skeleton

temporal bone squamous part hypoplasia ( J:214092 )

• squamosal bone is slightly hypoplastic

mandible hypoplasia ( J:214092 )

• proximal mandible is slightly hypoplastic

decreased maxillary shelf size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

decreased palatine bone horizontal plate size ( J:214092 )

• the palatal processes of the palatine and maxilla appear to fuse normally along the midline, although both structures are smaller

absent middle ear ossicles ( J:214092 )

• the middle-ear ossicles are either hypoplastic or absent

middle ear ossicle hypoplasia ( J:214092 )

• the middle-ear ossicles are either hypoplastic or absent, although portions of the alisphenoid appear better developed

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

Genotype
MGI:6720292

cn23

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Rr80^em1Jwsk/Rr80⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C3H * C57BL/6J * FVB/NJ

craniofacial

abnormal mandible morphology ( J:306395 )

• exacerbated compared with wild-type enhancer cluster 1.45

mandibular condyloid process hypoplasia ( J:306395 )

short mandible ( J:306395 )

growth/size/body

postnatal growth retardation ( J:306395 )

skeleton

abnormal mandible morphology ( J:306395 )

• exacerbated compared with wild-type enhancer cluster 1.45

mandibular condyloid process hypoplasia ( J:306395 )

short mandible ( J:306395 )

Genotype
MGI:7341534

cn24

• Allelic Composition: Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S/Sv * 129X1/SvJ * C57BL/6J

embryo

embryo phenotype ( J:279139 )

N • lineage-tracing analysis showed no apparent defects in cranial, cardiac and enteric neural crest cell migration

cellular

cellular phenotype ( J:279139 )

N • lineage-tracing analysis showed no apparent defects in cranial, cardiac and enteric neural crest cell migration

Genotype
MGI:7343722

cn25

• Allelic Composition: Vegfa^tm2Gne/Vegfa^tm2Gne; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129/Sv * C3H * C57BL/6

craniofacial

abnormal mandible morphology ( J:309228 )

• at E14.5, E16.5, and E18.5, intramembranous ossification is reduced in the anterior, middle and posterior mandible

• however, no micrognathia is observed

abnormal maxilla morphology ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior maxilla

abnormal palatal mesenchymal cell proliferation ( J:309228 )

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

abnormal secondary palate development ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

• vascularization of the palatal shelves is impaired, with reduced vessel formation at E13.5, less vascular channels and decreased vascular branching at E14.5, and markedly reduced PECAM localization within both anterior and posterior palatal shelves at E15.5

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

• apoptosis remains normal during palatogenesis from E12.5 to E15.5

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

abnormal palatal shelf elevation ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation and elevation above the tongue whereas control shelves have elevated and apposed

• at E15.5, palatal shelves are inconsistently elevated whereas control shelves are undergoing fusion as indicated by dissolution of the medial edge epithelium (MEE)

palatal shelves fail to meet at midline ( J:309228 )

decreased palatal shelf size ( J:309228 )

• at E12.5 and 13.5, palatal shelf width, defined as the length from the hinge of the palatal shelf to the tip of the medial edge epithelium (MEE), is significantly reduced both anteriorly and posteriorly

palatal shelf hypoplasia ( J:309228 )

• at E15.5, palatal shelves are hypoplastic

cardiovascular system

abnormal vascular development ( J:309228 )

• at E13.5, E14.5 and E15.5, PECAM immunohistochemistry showed reduced vessel development and branching in both the anterior and posterior palatal shelves

poor arterial differentiation ( J:309228 )

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

skeleton

abnormal mandible morphology ( J:309228 )

• at E14.5, E16.5, and E18.5, intramembranous ossification is reduced in the anterior, middle and posterior mandible

• however, no micrognathia is observed

abnormal maxilla morphology ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior maxilla

abnormal intramembranous bone ossification ( J:309228 )

• at E14.5, mesenchymal condensations within the maxilla ossification centers are reduced in size

• at E16.5, maxillary and palatine bones exhibit less ossification and poor bony ingrowth

• at E18.5, ossification of the maxillary bone is insufficient

• at E14.5, E16.5, and E18.5, ossification is reduced in the anterior, middle and posterior mandible

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

digestive/alimentary system

abnormal palatal mesenchymal cell proliferation ( J:309228 )

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

abnormal secondary palate development ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

• vascularization of the palatal shelves is impaired, with reduced vessel formation at E13.5, less vascular channels and decreased vascular branching at E14.5, and markedly reduced PECAM localization within both anterior and posterior palatal shelves at E15.5

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

• apoptosis remains normal during palatogenesis from E12.5 to E15.5

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

abnormal palatal shelf elevation ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation and elevation above the tongue whereas control shelves have elevated and apposed

• at E15.5, palatal shelves are inconsistently elevated whereas control shelves are undergoing fusion as indicated by dissolution of the medial edge epithelium (MEE)

palatal shelves fail to meet at midline ( J:309228 )

decreased palatal shelf size ( J:309228 )

• at E12.5 and 13.5, palatal shelf width, defined as the length from the hinge of the palatal shelf to the tip of the medial edge epithelium (MEE), is significantly reduced both anteriorly and posteriorly

palatal shelf hypoplasia ( J:309228 )

• at E15.5, palatal shelves are hypoplastic

growth/size/body

abnormal palatal mesenchymal cell proliferation ( J:309228 )

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

abnormal secondary palate development ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation

• at E14.5 and E15.5, cell proliferation is significantly reduced within the anterior and posterior palatal shelves

• vascularization of the palatal shelves is impaired, with reduced vessel formation at E13.5, less vascular channels and decreased vascular branching at E14.5, and markedly reduced PECAM localization within both anterior and posterior palatal shelves at E15.5

• vascular smooth muscle investment of the palatine artery is absent at E14.5 and appears reduced and only seen 50% of the time at E15.5

• apoptosis remains normal during palatogenesis from E12.5 to E15.5

abnormal palatal shelf bone ossification ( J:309228 )

• at E14.5, E16.5 and E18.5, intramembranous ossification is reduced in the anterior and posterior palatal shelves

abnormal palatal shelf elevation ( J:309228 )

• at E14.5, palatal shelves fail to undergo elongation and elevation above the tongue whereas control shelves have elevated and apposed

• at E15.5, palatal shelves are inconsistently elevated whereas control shelves are undergoing fusion as indicated by dissolution of the medial edge epithelium (MEE)

palatal shelves fail to meet at midline ( J:309228 )

decreased palatal shelf size ( J:309228 )

• at E12.5 and 13.5, palatal shelf width, defined as the length from the hinge of the palatal shelf to the tip of the medial edge epithelium (MEE), is significantly reduced both anteriorly and posteriorly

palatal shelf hypoplasia ( J:309228 )

• at E15.5, palatal shelves are hypoplastic

Genotype
MGI:5604134

cn26

• 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:5604135

cn27

• Allelic Composition: Hand1^tm4Abfi/Hand1⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

neonatal lethality ( J:214092 )

craniofacial

abnormal alisphenoid bone morphology ( J:214092 )

• absence of at least a portion of the ala temporalis portion of the alisphenoid

temporal bone squamous part hypoplasia ( J:214092 )

• the squamosal bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

small mandible ( J:214092 )

• proximal mandible appears slightly smaller

premaxilla hypoplasia ( J:214092 )

• the premaxilla bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

nasal bone hypoplasia ( J:214092 )

• the nasal bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused 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 )

• the midline cleft of the maxilla is more severe than in conditional heterozygous Hand1^tm3Abfi mice, with the defect extending into the parietal bones

digestive/alimentary system

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

nasal bone hypoplasia ( J:214092 )

• the nasal bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused 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 )

• the midline cleft of the maxilla is more severe than in conditional heterozygous Hand1^tm3Abfi mice, with the defect extending into the parietal bones

respiratory system

nasal bone hypoplasia ( J:214092 )

• the nasal bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

absent nasal septum ( J:214092 )

skeleton

abnormal alisphenoid bone morphology ( J:214092 )

• absence of at least a portion of the ala temporalis portion of the alisphenoid

temporal bone squamous part hypoplasia ( J:214092 )

• the squamosal bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

small mandible ( J:214092 )

• proximal mandible appears slightly smaller

premaxilla hypoplasia ( J:214092 )

• the premaxilla bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

nasal bone hypoplasia ( J:214092 )

• the nasal bones are highly hypoplastic but are better formed than in compound heterozygous Hand1^tm2Eno/ Hand1^tm4Abfi conditional mice

abnormal nasal capsule morphology ( J:214092 )

• nasal capsule remains unfused at E18.5

Genotype
MGI:6887946

cn28

• Allelic Composition: C2cd3^em2Brgm/C2cd3^em2Brgm; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: C3H * C57BL/6

craniofacial

cleft palate ( J:308674 )

abnormal tongue morphology ( J:308674 )

• dysmorphic tongue

cellular

abnormal cilium physiology ( J:308674 )

• increased Gli3FL/Gli3R ratio indicating the cilia are functionally impaired

skeleton

delayed bone ossification ( J:308674 )

• delayed ossification of the palatine bone at E17.5

digestive/alimentary system

cleft palate ( J:308674 )

abnormal tongue morphology ( J:308674 )

• dysmorphic tongue

growth/size/body

cleft palate ( J:308674 )

abnormal tongue morphology ( J:308674 )

• dysmorphic tongue

Genotype
MGI:6887948

cn29

• Allelic Composition: C2cd3^{tm1c(EUCOMM)Wtsi}/C2cd3^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: C3H * C57BL/6

craniofacial

abnormal facial morphology ( J:308674 )

• midline widening detected at e11.5 which is exacerbated at E15.5

cleft palate ( J:308674 )

tongue hypoplasia ( J:308674 )

cellular

abnormal cilium physiology ( J:308674 )

• increased Gli3FL/Gli3R ratio indicating the cilia are functionally impaired

skeleton

delayed bone ossification ( J:308674 )

• delayed ossification of the palatine and sphenoid bones at E17.5

digestive/alimentary system

cleft palate ( J:308674 )

tongue hypoplasia ( J:308674 )

growth/size/body

abnormal facial morphology ( J:308674 )

• midline widening detected at e11.5 which is exacerbated at E15.5

cleft palate ( J:308674 )

tongue hypoplasia ( J:308674 )

Genotype
MGI:7437965

cn30

• Allelic Composition: E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺; Snrpb^em1Lajm/Snrpb⁺
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6J * CD1

mortality/aging

neonatal lethality, complete penetrance ( J:326544 )

• no heterozygotes were found at P1 or P1 but 5 were found at P0

lethality throughout fetal growth and development, incomplete penetrance ( J:326544 )

• fewer than expected found at E14.5 and E17.5

skeleton

abnormal cranium morphology ( J:326544 )

abnormal metopic suture morphology ( J:326544 )

• heterotopic ossification in 1 pup at P0

basisphenoid bone hypoplasia ( J:326544 )

• in some embryos

• hypoplastic and asymmetric in 3 pups at P0

Meckel's cartilage hypoplasia ( J:326544 )

• at E14.5 and E17.5

frontal bone hypoplasia ( J:326544 )

• at E14.5 and E17.5 in 5 embryos

interparietal bone hypoplasia ( J:326544 )

• in 8 embryos at E14.5 and E17.5

parietal bone hypoplasia ( J:326544 )

• in 8 embryos at E14.5 and E17.5

absent alisphenoid bone ( J:326544 )

• at E14.5 and E17.5

abnormal temporal bone morphology ( J:326544 )

• absent at E14.5 and E17.5

small temporal bone squamous part ( J:326544 )

• in 3 pups

absent zygomatic arch ( J:326544 )

• fails to form in some embryos

absent hyoid bone ( J:326544 )

• hypoplastic or absent

hyoid bone hypoplasia ( J:326544 )

• hypoplastic or absent

abnormal jaw morphology ( J:326544 )

• distal ends are abnormally shaped

abnormal mandible morphology ( J:326544 )

• cleft in the mandible in 25% of embryos at E12.5

• mandible is bilaterally smaller and asymmetrical in some embryos at E14.5 and E17.5

• proximal elements are absent

absent mandibular angle ( J:326544 )

absent mandibular condyloid process ( J:326544 )

absent mandibular coronoid process ( J:326544 )

mandible hypoplasia ( J:326544 )

• hypoplastic and cleft at E14.5 in 4 of 12 embryos

abnormal premaxilla morphology ( J:326544 )

• clefts of the pre-maxillary cartilage and bone

• at P0 a single pup had a curved but closed premaxilla

maxilla hypoplasia ( J:326544 )

• hypoplastic and cleft at E14.5 in 4 of 12 embryos

nasal bone hypoplasia ( J:326544 )

• at E14.5 and E17.5 in 5 embryos

• also show clefts in the nasal cartilage and bones

domed cranium ( J:326544 )

• dome-shaped head in 3 of 12 at E14.5

abnormal tracheal cartilage morphology ( J:326544 )

• missing

ectopic cartilage ( J:326544 )

• ectopic unidentifiable cartilage and bones in the middle ear

ectopic bone ( J:326544 )

• ectopic unidentifiable cartilage and bones in the middle ear

endocrine/exocrine glands

athymia ( J:326544 )

• in 1 embryos at E17.5

cellular

abnormal DNA-templated transcription ( J:326544 )

• increase in exon skipping and intron retention in cells from heads of E9.0 embryos

cardiovascular system

absent aorticopulmonary septum ( J:326544 )

• fails to differentiate by E17.5 in one embryo

homeostasis/metabolism

edema ( J:326544 )

• in 19% of embryos at E12.5

• subepidermal edema in 4 of 12 of embryos at E14.5

digestive/alimentary system

cleft palate ( J:326544 )

• at E14.5 and E17.5

• a single pup at P0 had a cleft in the premaxilla and was missing the palatine shelves but no bony palate defects were found in 3 other pups

respiratory system

abnormal nose morphology ( J:326544 )

• nasal cleft in 3 of 12 embryos at E14.5

nasal bone hypoplasia ( J:326544 )

• at E14.5 and E17.5 in 5 embryos

• also show clefts in the nasal cartilage and bones

absent nasal septum ( J:326544 )

• in some embryos at E14.5

abnormal nasopharynx morphology ( J:326544 )

• the nasopharyngeal cavity is not formed in some embryos at E14.5

abnormal tracheal cartilage morphology ( J:326544 )

• missing

embryo

abnormal embryonic tissue morphology ( J:326544 )

• subepidermal swelling in 66% of embryos at E11.5

• at E17.5 no phenotypically normal embryos are found unlike at earlier time points

pharyngeal arch hypoplasia ( J:326544 )

• in 74% of embryos at E10.5

first pharyngeal arch hypoplasia ( J:326544 )

• in 66% of embryos at E11.5

• in 19% of embryos at E12.5

behavior/neurological

absent gastric milk in neonates ( J:326544 )

• in most neonates

nervous system

hindbrain hypoplasia ( J:326544 )

• in 35% and 74% of embryos at E9.5 and E10.5

midbrain hypoplasia ( J:326544 )

• in 35% and 74% of embryos at E9.5 and E10.5

• in 25% of embryos at E12.5

abnormal forebrain morphology ( J:326544 )

• swelling in 66% at E11.5

• abnormal in 25% of embryos at E12.5

enlarged lateral ventricles ( J:326544 )

• at E14.5 and E17.5 in 1 embryo at each age

thin cerebral cortex ( J:326544 )

• at E14.5 and E17.5 in 1 embryo at each age

abnormal cranial ganglia morphology ( J:326544 )

• reduced in size with abnormal projections into the pharyngeal arches at E10.5 in some embryos

abnormal geniculate ganglion morphology ( J:326544 )

• the proximal portion is thicker

abnormal vestibular ganglion morphology ( J:326544 )

• the proximal portion is thicker

abnormal glossopharyngeal nerve morphology ( J:326544 )

• thicker in the proximal region before the pharyngeal arch, has an ectopic projection into pharyngeal arch 2, and reduced projection into pharyngeal arch 3

abnormal trigeminal nerve morphology ( J:326544 )

• ectopic projection

abnormal mandibular nerve morphology ( J:326544 )

• reduced and appears to have formed ventral to the first arch at E10.5 in some embryos

abnormal maxillary nerve morphology ( J:326544 )

• disorganized and missing at E10.5 in some embryos

abnormal ophthalmic nerve morphology ( J:326544 )

• reduced and fails to extend over the lens at E10.5 in some embryos

abnormal vagus nerve morphology ( J:326544 )

• abnormal bundle at the distal end with reduced projections into the heart

small dorsal root ganglion ( J:326544 )

• small and bifurcated at the proximal end

hearing/vestibular/ear

small ears ( J:326544 )

• in 4 of 5 neonates

• in 3 of 12 embryos at E14.5

absent tympanic ring ( J:326544 )

craniofacial

abnormal cranium morphology ( J:326544 )

abnormal metopic suture morphology ( J:326544 )

• heterotopic ossification in 1 pup at P0

basisphenoid bone hypoplasia ( J:326544 )

• in some embryos

• hypoplastic and asymmetric in 3 pups at P0

Meckel's cartilage hypoplasia ( J:326544 )

• at E14.5 and E17.5

frontal bone hypoplasia ( J:326544 )

• at E14.5 and E17.5 in 5 embryos

interparietal bone hypoplasia ( J:326544 )

• in 8 embryos at E14.5 and E17.5

parietal bone hypoplasia ( J:326544 )

• in 8 embryos at E14.5 and E17.5

absent alisphenoid bone ( J:326544 )

• at E14.5 and E17.5

abnormal temporal bone morphology ( J:326544 )

• absent at E14.5 and E17.5

small temporal bone squamous part ( J:326544 )

• in 3 pups

absent zygomatic arch ( J:326544 )

• fails to form in some embryos

absent hyoid bone ( J:326544 )

• hypoplastic or absent

hyoid bone hypoplasia ( J:326544 )

• hypoplastic or absent

abnormal jaw morphology ( J:326544 )

• distal ends are abnormally shaped

abnormal mandible morphology ( J:326544 )

• cleft in the mandible in 25% of embryos at E12.5

• mandible is bilaterally smaller and asymmetrical in some embryos at E14.5 and E17.5

• proximal elements are absent

absent mandibular angle ( J:326544 )

absent mandibular condyloid process ( J:326544 )

absent mandibular coronoid process ( J:326544 )

mandible hypoplasia ( J:326544 )

• hypoplastic and cleft at E14.5 in 4 of 12 embryos

abnormal premaxilla morphology ( J:326544 )

• clefts of the pre-maxillary cartilage and bone

• at P0 a single pup had a curved but closed premaxilla

maxilla hypoplasia ( J:326544 )

• hypoplastic and cleft at E14.5 in 4 of 12 embryos

domed cranium ( J:326544 )

• dome-shaped head in 3 of 12 at E14.5

abnormal frontonasal prominence morphology ( J:326544 )

• cleft in the frontonasal prominence in 25% of embryos at E12.5

absent frontonasal prominence ( J:326544 )

• in 66% of embryos at E11.5

frontonasal prominence hypoplasia ( J:326544 )

• at E10.5

• hypoplastic and cleft at E12.5 in 25% of embryos

• hypoplastic and cleft frontonasal region in 4 of 12 embryos at E14.5

mandibular prominence hypoplasia ( J:326544 )

• in 74% of embryos at E10.5

absent maxillary prominence ( J:326544 )

• in 66% of embryos at E11.5

maxillary prominence hypoplasia ( J:326544 )

• in 74% of embryos at E10.5

• hypoplastic and cleft in 25% of embryos at E12.5

pharyngeal arch hypoplasia ( J:326544 )

• in 74% of embryos at E10.5

first pharyngeal arch hypoplasia ( J:326544 )

• in 66% of embryos at E11.5

• in 19% of embryos at E12.5

cleft palate ( J:326544 )

• at E14.5 and E17.5

• a single pup at P0 had a cleft in the premaxilla and was missing the palatine shelves but no bony palate defects were found in 3 other pups

abnormal nose morphology ( J:326544 )

• nasal cleft in 3 of 12 embryos at E14.5

nasal bone hypoplasia ( J:326544 )

• at E14.5 and E17.5 in 5 embryos

• also show clefts in the nasal cartilage and bones

absent nasal septum ( J:326544 )

• in some embryos at E14.5

short snout ( J:326544 )

• in 4 of 5 neonates

abnormal head shape ( J:326544 )

• in 4 of 5 neonates

small ears ( J:326544 )

• in 4 of 5 neonates

• in 3 of 12 embryos at E14.5

growth/size/body

cleft palate ( J:326544 )

• at E14.5 and E17.5

• a single pup at P0 had a cleft in the premaxilla and was missing the palatine shelves but no bony palate defects were found in 3 other pups

abnormal nose morphology ( J:326544 )

• nasal cleft in 3 of 12 embryos at E14.5

nasal bone hypoplasia ( J:326544 )

• at E14.5 and E17.5 in 5 embryos

• also show clefts in the nasal cartilage and bones

absent nasal septum ( J:326544 )

• in some embryos at E14.5

short snout ( J:326544 )

• in 4 of 5 neonates

abnormal head shape ( J:326544 )

• in 4 of 5 neonates

small ears ( J:326544 )

• in 4 of 5 neonates

• in 3 of 12 embryos at E14.5

abnormal head development ( J:326544 )

• absence of the ventral portion of the head and face in 19% of embryos at E12.5

• absence of the ventral portion of the head and face in 4 of 12 embryos at E14.5

• many neural crest derived bones and cartilages are hypoplastic or missing in embryos at E14.5 and E17.5

immune system

athymia ( J:326544 )

• in 1 embryos at E17.5

hematopoietic system

athymia ( J:326544 )

• in 1 embryos at E17.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebrocostomandibular syndrome		DOID:0111248	OMIM:117650	J:326544

Genotype
MGI:6885557

cn31

• Allelic Composition: Ankrd11^{tm1c(EUCOMM)Wtsi}/Ankrd11^{tm1c(EUCOMM)Wtsi}; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N
• Cell Lines: EPD0678_1_F03

mortality/aging

perinatal lethality, complete penetrance ( J:306391 )

• mice die at birth

craniofacial

abnormal craniofacial morphology ( J:306391 )

• severe craniofacial phenotypes observed at P0

abnormal basicranium morphology ( J:306391 )

• reduced ossification of the anterior cranial base (presphenoid and basisphenoid)

• however, more posterior, mesoderm-derived components of the cranial base (basioccipital bone) are unaffected

abnormal neurocranium morphology ( J:306391 )

• reduced calvarial growth, evident as reduction in calvarial microvasculature

large anterior fontanelle ( J:306391 )

• persistent anterior fontanelle

impaired ossification of basisphenoid bone ( J:306391 )

small frontal bone ( J:306391 )

• 83% reduction in frontal bone volume

frontal bone hypoplasia ( J:306391 )

small parietal bone ( J:306391 )

• 76% reduction in parietal bone volume

absent pterygoid process ( J:306391 )

• formation of pterygoid wings is largely absent

small mandible ( J:306391 )

• 39% reduction in mandible volume

micrognathia ( J:306391 )

• severe micrognathia at P0

retrognathia ( J:306391 )

abnormal palatine bone morphology ( J:306391 )

• reduction in palatine bone ossification

domed cranium ( J:306391 )

abnormal palatal mesenchymal cell proliferation ( J:306391 )

• 40% decrease in mesenchymal proliferation in the oral domain of palatal shelves at E13.5, with disorganized mesenchymal cells lining the shelf epithelium

• however, no significant apoptosis observed between E12.5-E13.5

abnormal palatal shelf morphology ( J:306391 )

• 15% increase in cell density in the nasal domain of palatal shelves at E13.5, with no differences observed in the oral domain

palatal shelves fail to meet at midline ( J:306391 )

• palatal shelves fail to meet and fuse

• however, palatal shelf elevation appears normal

palatal shelf hypoplasia ( J:306391 )

• palatal shelves are hypoplastic and dysmorphic as early as E12.5

• tip of the palatal shelf remains hypoplastic at later developmental stages

triangular face ( J:306391 )

• triangular shape face

midface hypoplasia ( J:306391 )

• variable midfacial hypoplasia

abnormal snout skin morphology ( J:306391 )

• snout shows loss of black pigment

cleft palate ( J:306391 )

• fully penetrant cleft palate

cleft hard palate ( J:306391 )

• clefting of hard palate at P0

decreased tongue size ( J:306391 )

• shorter and thinner tongue at P0

tongue hypoplasia ( J:306391 )

short tongue ( J:306391 )

growth/size/body

abnormal head morphology ( J:306391 )

• head appears paler with a more domed shape

abnormal palatal mesenchymal cell proliferation ( J:306391 )

• 40% decrease in mesenchymal proliferation in the oral domain of palatal shelves at E13.5, with disorganized mesenchymal cells lining the shelf epithelium

• however, no significant apoptosis observed between E12.5-E13.5

abnormal palatal shelf morphology ( J:306391 )

• 15% increase in cell density in the nasal domain of palatal shelves at E13.5, with no differences observed in the oral domain

palatal shelves fail to meet at midline ( J:306391 )

• palatal shelves fail to meet and fuse

• however, palatal shelf elevation appears normal

palatal shelf hypoplasia ( J:306391 )

• palatal shelves are hypoplastic and dysmorphic as early as E12.5

• tip of the palatal shelf remains hypoplastic at later developmental stages

triangular face ( J:306391 )

• triangular shape face

midface hypoplasia ( J:306391 )

• variable midfacial hypoplasia

abnormal snout skin morphology ( J:306391 )

• snout shows loss of black pigment

cleft palate ( J:306391 )

• fully penetrant cleft palate

cleft hard palate ( J:306391 )

• clefting of hard palate at P0

decreased tongue size ( J:306391 )

• shorter and thinner tongue at P0

tongue hypoplasia ( J:306391 )

short tongue ( J:306391 )

skeleton

abnormal basicranium morphology ( J:306391 )

• reduced ossification of the anterior cranial base (presphenoid and basisphenoid)

• however, more posterior, mesoderm-derived components of the cranial base (basioccipital bone) are unaffected

abnormal neurocranium morphology ( J:306391 )

• reduced calvarial growth, evident as reduction in calvarial microvasculature

large anterior fontanelle ( J:306391 )

• persistent anterior fontanelle

small frontal bone ( J:306391 )

• 83% reduction in frontal bone volume

frontal bone hypoplasia ( J:306391 )

small parietal bone ( J:306391 )

• 76% reduction in parietal bone volume

absent pterygoid process ( J:306391 )

• formation of pterygoid wings is largely absent

small mandible ( J:306391 )

• 39% reduction in mandible volume

micrognathia ( J:306391 )

• severe micrognathia at P0

retrognathia ( J:306391 )

abnormal palatine bone morphology ( J:306391 )

• reduction in palatine bone ossification

domed cranium ( J:306391 )

decreased osteoclast cell number ( J:306391 )

• 99% reduction in TRAP-positive regions in the maxilla, along with an 85% reduction in the mandible, and a 99.5% reduction in the calvaria

abnormal bone collagen fibril morphology ( J:306391 )

• alterations in the extent of collagen fibril interconnection and orientation in the maxilla, calvaria and mandible at P0

abnormal osteocyte morphology ( J:306391 )

• increased number of poorly aligned osteocytes with plump (immature) morphology in the maxilla, calvaria and mandible at P0

• reduction in Sost (sclerostin)-positive cells in the maxillary bone at P0, suggesting delayed osteocyte maturation

decreased bone trabecula number ( J:306391 )

• overall reduction in trabeculation in the maxilla, calvaria and mandible

abnormal intramembranous bone ossification ( J:306391 )

• all intramembranously formed orofacial bones are decreased in size, resulting in an underdeveloped midface and mandible

impaired ossification of basisphenoid bone ( J:306391 )

delayed intramembranous bone ossification ( J:306391 )

• intramembranous bones exhibit features of delayed maturation

decreased bone ossification ( J:306391 )

• reduced ossification of the palatine bones and the anterior cranial base (presphenoid and sphenoid)

• severely reduced ossification of anterior cranial bones; bones fail to cover most of the cranium at birth

• several primary ossification centers fail to expand and/or fuse

• however, interparietal, occipital and basioccipital bones are not significantly affected

abnormal bone remodeling ( J:306391 )

• bone remodeling is severely impaired at birth

• single-layered bone observed in the calvaria, indicating decreased or defective bone remodeling

decreased bone resorption ( J:306391 )

• nearly complete lack of bone resorption and, by extension, remodeling in the calvaria

vision/eye

eyelids open at birth ( J:306391 )

• partially open eyelids at P0

cardiovascular system

abnormal cranial blood vasculature morphology ( J:306391 )

• reduction in calvarial microvasculature

digestive/alimentary system

abnormal palatal mesenchymal cell proliferation ( J:306391 )

• 40% decrease in mesenchymal proliferation in the oral domain of palatal shelves at E13.5, with disorganized mesenchymal cells lining the shelf epithelium

• however, no significant apoptosis observed between E12.5-E13.5

abnormal palatal shelf morphology ( J:306391 )

• 15% increase in cell density in the nasal domain of palatal shelves at E13.5, with no differences observed in the oral domain

palatal shelves fail to meet at midline ( J:306391 )

• palatal shelves fail to meet and fuse

• however, palatal shelf elevation appears normal

palatal shelf hypoplasia ( J:306391 )

• palatal shelves are hypoplastic and dysmorphic as early as E12.5

• tip of the palatal shelf remains hypoplastic at later developmental stages

cleft palate ( J:306391 )

• fully penetrant cleft palate

cleft hard palate ( J:306391 )

• clefting of hard palate at P0

decreased tongue size ( J:306391 )

• shorter and thinner tongue at P0

tongue hypoplasia ( J:306391 )

short tongue ( J:306391 )

hematopoietic system

decreased osteoclast cell number ( J:306391 )

• 99% reduction in TRAP-positive regions in the maxilla, along with an 85% reduction in the mandible, and a 99.5% reduction in the calvaria

immune system

decreased osteoclast cell number ( J:306391 )

• 99% reduction in TRAP-positive regions in the maxilla, along with an 85% reduction in the mandible, and a 99.5% reduction in the calvaria

integument

abnormal snout skin morphology ( J:306391 )

• snout shows loss of black pigment

pigmentation

hypopigmentation ( J:306391 )

• snout shows loss of black pigment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
KBG syndrome		DOID:14780	OMIM:148050	J:306391

Genotype
MGI:7336829

cn32

• Allelic Composition: Ankrd11^{tm1c(EUCOMM)Wtsi}/Ankrd11⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: C3H * C57BL/6 * C57BL/6N
• Cell Lines: EPD0678_1_F03

craniofacial

wide metopic suture ( J:306391 )

• open posterior frontal suture

abnormal neurocranium morphology ( J:306391 )

• calvarial defect surrounding the posterior frontal suture

large anterior fontanelle ( J:306391 )

• persistent anterior fontanelle

abnormal frontal bone morphology ( J:306391 )

• hard tissue anomalies in frontal bone

abnormal pterygoid bone morphology ( J:306391 )

• slight change in pterygoid bone morphology seen in ortho-slices anterior to the coronal suture; angle of the medial aspect of the pterygoid bone relative to the ventrolateral is altered

enlarged neurocranium ( J:306391 )

• expanded cranial vault

abnormal mandible morphology ( J:306391 )

• variable position of the mandible with respect to the skull (excluded from analysis)

narrow face ( J:306391 )

• reduced facial width

abnormal midface morphology ( J:306391 )

• reduced midfacial width

midface hypoplasia ( J:306391 )

• mild midfacial hypoplasia

abnormal nose morphology ( J:306391 )

• hypoplasia of the nasal region

skeleton

wide metopic suture ( J:306391 )

• open posterior frontal suture

abnormal neurocranium morphology ( J:306391 )

• calvarial defect surrounding the posterior frontal suture

large anterior fontanelle ( J:306391 )

• persistent anterior fontanelle

abnormal frontal bone morphology ( J:306391 )

• hard tissue anomalies in frontal bone

abnormal pterygoid bone morphology ( J:306391 )

• slight change in pterygoid bone morphology seen in ortho-slices anterior to the coronal suture; angle of the medial aspect of the pterygoid bone relative to the ventrolateral is altered

enlarged neurocranium ( J:306391 )

• expanded cranial vault

abnormal mandible morphology ( J:306391 )

• variable position of the mandible with respect to the skull (excluded from analysis)

growth/size/body

narrow face ( J:306391 )

• reduced facial width

abnormal midface morphology ( J:306391 )

• reduced midfacial width

midface hypoplasia ( J:306391 )

• mild midfacial hypoplasia

abnormal nose morphology ( J:306391 )

• hypoplasia of the nasal region

respiratory system

abnormal nose morphology ( J:306391 )

• hypoplasia of the nasal region

mortality/aging

mortality/aging ( J:306391 )

N • mice survive into adulthood

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
KBG syndrome		DOID:14780	OMIM:148050	J:306391