Phenotypes associated with this allele

• Allele Symbol: Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis
• Allele Name: transgene insertion 35-1, Yuji Mishina
• Allele ID: MGI:3821884
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0	involves: C57BL/6 * DBA/2	MGI:3821886
cn2	Tg(CAG-cre/Esr1*)5Amc/0 Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0	involves: C57BL/6 * CBA * DBA/2	MGI:3821885
cn3	Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0 Tg(KRT14-cre)1Amc/0	involves: C57BL/6 * CBA * DBA/2	MGI:7461096

Genotype
MGI:3821886

cn1

• Allelic Composition: Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

skeleton

abnormal skeleton morphology ( J:142253 )

• by P30, limbs injected with adenovirus cre at P11 exhibit bony calluses encasing the tibia and fibula as well as fused with the pelvis and femur rendering hip, knee and ankle joints immobile unlike in similarly treated wild-type mice

• however, treatment of adenovirus cre exposed mice with LDN-193189, an inhibitor of BMP type I receptors, or dexamethasone reduces ectopic calcifications

decreased joint mobility ( J:142253 )

• by P30, limbs injected with adenovirus cre at P11 exhibit reduced mobility including loss of passive flexion in the hip, knee and ankle under aesthesia unlike in similarly treated wild-type mice

muscle

myositis ( J:142253 )

• regardless of LDN-193189 treatment, limbs injected with adenovirus cre at P11 exhibit mononuclear cell infiltration and myocyte edema in tissues undergoing recombination unlike in similarly treated wild-type mice

immune system

myositis ( J:142253 )

• regardless of LDN-193189 treatment, limbs injected with adenovirus cre at P11 exhibit mononuclear cell infiltration and myocyte edema in tissues undergoing recombination unlike in similarly treated wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fibrodysplasia ossificans progressiva		DOID:13374	OMIM:135100	J:142253

Genotype
MGI:3821885

cn2

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0
• Genetic Background: involves: C57BL/6 * CBA * DBA/2

skeleton

skeleton phenotype ( J:142253 )

N • unlike mice treated with adenoviral cre, tamoxifen treated mice exhibit normal ossification and joint mobility

abnormal skeleton morphology ( J:142253 )

• tamoxifen treated mice injected with a control adenovirus exhibit decreased limb motion and small ectopic calcifications by P14

muscle

muscle phenotype ( J:142253 )

N • unlike mice treated with adenoviral cre, tamoxifen treated mice exhibit normal myocytes

Genotype
MGI:7461096

cn3

• Allelic Composition: Tg(CAG-LacZ,-ACVR1*,-EGFP)35-1Mis/0; Tg(KRT14-cre)1Amc/0
• Genetic Background: involves: C57BL/6 * CBA * DBA/2

mortality/aging

neonatal lethality, complete penetrance ( J:233662 )

• all newborn pups die within 24 h of birth

behavior/neurological

absent gastric milk in neonates ( J:233662 )

• all newborn pups lack milk in their stomachs

craniofacial

abnormal primary and secondary palatal fusion ( J:233662 )

• the primary palate fails to fuse with the secondary palate

abnormal secondary palate development ( J:233662 )

• at E18.5, palatal shelves of the anterior secondary palate fail to fuse with each other and with the nasal septum

• in the middle part of the secondary palate, the fusion of mesenchymal tissue is impaired by the presence of an epithelial seam

• an epithelial cyst-like tissue is detected intermittently at the midline of hard palate and soft palate

persistence of medial edge epithelium during palatal shelf fusion ( J:233662 )

• although medial edge epithelium (MEE) seam formation is normal at E14.5, the MEE seam is not degraded at E15.5, unlike in control embryos

• TUNEL assays showed a significant reduction of apoptotic cells in MEE at E14.5; also, the expression level of cleaved caspase-3 is significantly reduced in MEE cells at E14.5

• downregulation of cell death is accompanied with upregulation of deltaNp63 in MEE at E14.5

• Ki67 staining showed a slight but significant increase of proliferating cells in MEE at E14.5 with continued ability of MEE cells to proliferate at E15.5

abnormal secondary palate morphology ( J:233662 )

• a white strip is found in the midline of the secondary palate including the soft palate

• however, cleft soft palate is not observed

abnormal hard palate morphology ( J:233662 )

• at E18.5, fusion of palatal mesenchyme in the hard palate is hampered by epithelial tissue

abnormal soft palate muscle morphology ( J:233662 )

• at E18.5, fusion of muscle fibers in the soft palate is hampered by epithelial tissue

abnormal tensor veli palatini muscle morphology ( J:233662 )

• at E18.5, an epithelial cyst-like tissue prevents the fusion of the tensor veli palatini muscle in the soft palate

submucous cleft palate ( J:233662 )

• mice develop submucous cleft palate (SMCP) without cleft soft palate

• SMCP is caused by abnormal medial edge epithelium persistence

digestive/alimentary system

abnormal primary and secondary palatal fusion ( J:233662 )

• the primary palate fails to fuse with the secondary palate

abnormal secondary palate development ( J:233662 )

• at E18.5, palatal shelves of the anterior secondary palate fail to fuse with each other and with the nasal septum

• in the middle part of the secondary palate, the fusion of mesenchymal tissue is impaired by the presence of an epithelial seam

• an epithelial cyst-like tissue is detected intermittently at the midline of hard palate and soft palate

persistence of medial edge epithelium during palatal shelf fusion ( J:233662 )

• although medial edge epithelium (MEE) seam formation is normal at E14.5, the MEE seam is not degraded at E15.5, unlike in control embryos

• TUNEL assays showed a significant reduction of apoptotic cells in MEE at E14.5; also, the expression level of cleaved caspase-3 is significantly reduced in MEE cells at E14.5

• downregulation of cell death is accompanied with upregulation of deltaNp63 in MEE at E14.5

• Ki67 staining showed a slight but significant increase of proliferating cells in MEE at E14.5 with continued ability of MEE cells to proliferate at E15.5

abnormal secondary palate morphology ( J:233662 )

• a white strip is found in the midline of the secondary palate including the soft palate

• however, cleft soft palate is not observed

abnormal hard palate morphology ( J:233662 )

• at E18.5, fusion of palatal mesenchyme in the hard palate is hampered by epithelial tissue

abnormal soft palate muscle morphology ( J:233662 )

• at E18.5, fusion of muscle fibers in the soft palate is hampered by epithelial tissue

abnormal tensor veli palatini muscle morphology ( J:233662 )

• at E18.5, an epithelial cyst-like tissue prevents the fusion of the tensor veli palatini muscle in the soft palate

submucous cleft palate ( J:233662 )

• mice develop submucous cleft palate (SMCP) without cleft soft palate

• SMCP is caused by abnormal medial edge epithelium persistence

growth/size/body

abnormal primary and secondary palatal fusion ( J:233662 )

• the primary palate fails to fuse with the secondary palate

abnormal secondary palate development ( J:233662 )

• at E18.5, palatal shelves of the anterior secondary palate fail to fuse with each other and with the nasal septum

• in the middle part of the secondary palate, the fusion of mesenchymal tissue is impaired by the presence of an epithelial seam

• an epithelial cyst-like tissue is detected intermittently at the midline of hard palate and soft palate

persistence of medial edge epithelium during palatal shelf fusion ( J:233662 )

• although medial edge epithelium (MEE) seam formation is normal at E14.5, the MEE seam is not degraded at E15.5, unlike in control embryos

• TUNEL assays showed a significant reduction of apoptotic cells in MEE at E14.5; also, the expression level of cleaved caspase-3 is significantly reduced in MEE cells at E14.5

• downregulation of cell death is accompanied with upregulation of deltaNp63 in MEE at E14.5

• Ki67 staining showed a slight but significant increase of proliferating cells in MEE at E14.5 with continued ability of MEE cells to proliferate at E15.5

abnormal secondary palate morphology ( J:233662 )

• a white strip is found in the midline of the secondary palate including the soft palate

• however, cleft soft palate is not observed

abnormal hard palate morphology ( J:233662 )

• at E18.5, fusion of palatal mesenchyme in the hard palate is hampered by epithelial tissue

abnormal soft palate muscle morphology ( J:233662 )

• at E18.5, fusion of muscle fibers in the soft palate is hampered by epithelial tissue

abnormal tensor veli palatini muscle morphology ( J:233662 )

• at E18.5, an epithelial cyst-like tissue prevents the fusion of the tensor veli palatini muscle in the soft palate

submucous cleft palate ( J:233662 )

• mice develop submucous cleft palate (SMCP) without cleft soft palate

• SMCP is caused by abnormal medial edge epithelium persistence

muscle

abnormal soft palate muscle morphology ( J:233662 )

• at E18.5, fusion of muscle fibers in the soft palate is hampered by epithelial tissue

abnormal tensor veli palatini muscle morphology ( J:233662 )

• at E18.5, an epithelial cyst-like tissue prevents the fusion of the tensor veli palatini muscle in the soft palate

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cleft palate		DOID:674		J:233662