Phenotypes Associated with This Genotype

Genotype
MGI:3697607

• Allelic Composition: Acvr1^tm1Vk/Acvr1^tm1.1Vk; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

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

mortality/aging

neonatal lethality, complete penetrance ( J:90988 )

• mutants that are born alive die during the first postnatal day

lethality throughout fetal growth and development, incomplete penetrance ( J:90988 , J:90453 )

• only 60% of expected numbers are recovered at birth, however the expected numbers are recovered at E14, indicating 40% lethality between E14 and birth (J:90988)

• about 40% die in utero (J:90453)

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:90988 )

• display abnormal regression of the pharyngeal arch arteries

abnormal sixth pharyngeal arch artery morphology ( J:90988 )

• at E11.5, the 6th arteries display bilaterally inappropriate regression

abnormal third pharyngeal arch artery morphology ( J:90988 )

• at E11.5, the 3rd arteries display bilaterally inappropriate regression

abnormal aortic arch morphology ( J:90988 )

• aortic arch defects

abnormal aortic arch and aortic arch branch attachment ( J:90988 )

• 77% exhibit either a short or missing brachiocephalic artery so that the right common carotid artery directly branches from the truncus arteriosus

retroesophageal right subclavian artery ( J:90988 )

• 15% penetrance

abnormal brachiocephalic trunk morphology ( J:90988 )

• 77% exhibit either a short or missing brachiocephalic artery

decreased cardiac neural crest cell number ( J:90988 )

• the distal outflow tract has reduced numbers of neural crest cells

absent cardiac neural crest cells ( J:90988 )

• the proximal outflow tract is essentially devoid of neural crest cells

impaired cardiac neural crest cell differentiation ( J:90988 )

• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient

abnormal cardiac outflow tract development ( J:90988 )

• the proximal outflow tract is essentially devoid of neural crest cells while the distal outflow tract has reduced numbers of neural crest cells

conotruncal ridge hypoplasia ( J:90988 )

• outflow tract cushions are reduced in size

persistent truncus arteriosus ( J:90988 )

• 100% penentrance or persistent truncus arteriosus type A2 (complete failure of outflow tract septation)

ventricular septal defect ( J:90988 )

• persistent truncus arteriosus is associated with a ventricular septation defect

enlarged heart ( J:90988 )

• 100% penetrance

increased heart right ventricle size ( J:90988 )

• 85% show hyperplastic right ventricle

nervous system

decreased cardiac neural crest cell number ( J:90988 )

• the distal outflow tract has reduced numbers of neural crest cells

absent cardiac neural crest cells ( J:90988 )

• the proximal outflow tract is essentially devoid of neural crest cells

impaired cardiac neural crest cell differentiation ( J:90988 )

• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient

craniofacial

abnormal pharyngeal arch artery morphology ( J:90988 )

• display abnormal regression of the pharyngeal arch arteries

abnormal sixth pharyngeal arch artery morphology ( J:90988 )

• at E11.5, the 6th arteries display bilaterally inappropriate regression

abnormal third pharyngeal arch artery morphology ( J:90988 )

• at E11.5, the 3rd arteries display bilaterally inappropriate regression

large anterior fontanelle ( J:90453 )

• enlarged frontal fontanels in newborns

abnormal Meckel's cartilage morphology ( J:90453 )

• the anterior cartilage derived from the distal extremity of Meckel's cartilage is absent

• anterior region of Meckel's cartilage displays retarded growth and also fails to fuse at E15

• display approximately a 3-fold reduction in proliferation of chondrocytes in the anterior and interior parts of Meckel's cartilage at E13

abnormal frontal bone squamous part morphology ( J:90453 )

• squamous parts of the frontal bones lack ossification towards the metopic region, resulting in enlarged frontal fontanels in newborns

absent retrotympanic process ( J:90453 )

• squamal bones lack the retrotympanic process

small temporal bone squamous part ( J:90453 )

• the temporal squama is smaller, lacking the lower portion with the mandibular fossa and its joint cartilage

absent temporal bone zygomatic process ( J:90453 )

• completely absent zygomatic process of the squamal bone

abnormal zygomatic arch morphology ( J:90453 )

• zygomatic arches are incomplete in newborns, with developed maxillary zygomatic process but completely absent jugal (zygomatic) bone and zygomatic process of the squamal bone

abnormal mandible morphology ( J:90453 )

abnormal mandibular fossa morphology ( J:90453 )

• the mandibular fossa and its joint cartilage are missing

small mandibular coronoid process ( J:90453 )

• coronoid process of the mandible is rudimentary in size

absent mandibular symphysis ( J:90453 )

• the mental symphysis is not formed resulting in persistently separate mandibular bones

absent temporomandibular joint ( J:90453 )

• the temporomandibular articulation is undetectable

mandible hypoplasia ( J:90453 )

• hypotrophic mandible is apparent as early as E14

short mandible ( J:90453 )

• mandible is about 40% shorter

absent zygomatic bone ( J:90453 )

• completely absent jugal (zygomatic) bone

abnormal malleus morphology ( J:90453 )

short malleus manubrium ( J:90453 )

• slightly shorter manubrium mallei

cleft secondary palate ( J:90453 )

• complete cleft of the secondary palate

abnormal palatal shelf elevation ( J:90453 )

• palatal shelves fail to elevate, either bilaterally or unilaterally, at E14

delayed palatal shelf elevation ( J:90453 )

• in newborns, the unfused palatal shelves are bilaterally elevated, indicating that cleft palate develops as a result of delayed, asynchronous elevation of palatal shelves

shortened head ( J:90453 )

• newborns have a shorter head

embryo

abnormal pharyngeal arch artery morphology ( J:90988 )

• display abnormal regression of the pharyngeal arch arteries

abnormal sixth pharyngeal arch artery morphology ( J:90988 )

• at E11.5, the 6th arteries display bilaterally inappropriate regression

abnormal third pharyngeal arch artery morphology ( J:90988 )

• at E11.5, the 3rd arteries display bilaterally inappropriate regression

decreased cardiac neural crest cell number ( J:90988 )

• the distal outflow tract has reduced numbers of neural crest cells

absent cardiac neural crest cells ( J:90988 )

• the proximal outflow tract is essentially devoid of neural crest cells

impaired cardiac neural crest cell differentiation ( J:90988 )

• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient

abnormal cardiac neural crest cell migration ( J:90988 )

• migration of mutant neural crest cells to the outflow tract is impaired

behavior/neurological

abnormal suckling behavior ( J:90453 )

• newborns lack milk in stomachs and fail to suckle

digestive/alimentary system

cleft secondary palate ( J:90453 )

• complete cleft of the secondary palate

abnormal palatal shelf elevation ( J:90453 )

• palatal shelves fail to elevate, either bilaterally or unilaterally, at E14

delayed palatal shelf elevation ( J:90453 )

• in newborns, the unfused palatal shelves are bilaterally elevated, indicating that cleft palate develops as a result of delayed, asynchronous elevation of palatal shelves

hearing/vestibular/ear

abnormal malleus morphology ( J:90453 )

short malleus manubrium ( J:90453 )

• slightly shorter manubrium mallei

skeleton

large anterior fontanelle ( J:90453 )

• enlarged frontal fontanels in newborns

abnormal frontal bone squamous part morphology ( J:90453 )

• squamous parts of the frontal bones lack ossification towards the metopic region, resulting in enlarged frontal fontanels in newborns

absent retrotympanic process ( J:90453 )

• squamal bones lack the retrotympanic process

small temporal bone squamous part ( J:90453 )

• the temporal squama is smaller, lacking the lower portion with the mandibular fossa and its joint cartilage

absent temporal bone zygomatic process ( J:90453 )

• completely absent zygomatic process of the squamal bone

abnormal zygomatic arch morphology ( J:90453 )

• zygomatic arches are incomplete in newborns, with developed maxillary zygomatic process but completely absent jugal (zygomatic) bone and zygomatic process of the squamal bone

abnormal mandible morphology ( J:90453 )

abnormal mandibular fossa morphology ( J:90453 )

• the mandibular fossa and its joint cartilage are missing

small mandibular coronoid process ( J:90453 )

• coronoid process of the mandible is rudimentary in size

absent mandibular symphysis ( J:90453 )

• the mental symphysis is not formed resulting in persistently separate mandibular bones

absent temporomandibular joint ( J:90453 )

• the temporomandibular articulation is undetectable

mandible hypoplasia ( J:90453 )

• hypotrophic mandible is apparent as early as E14

short mandible ( J:90453 )

• mandible is about 40% shorter

absent zygomatic bone ( J:90453 )

• completely absent jugal (zygomatic) bone

abnormal malleus morphology ( J:90453 )

short malleus manubrium ( J:90453 )

• slightly shorter manubrium mallei

abnormal cartilage morphology ( J:90453 )

• secondary cartilage of the mandibular condyle does not develop, making the temporomandibular articulation undetectable

• the secondary cartilage of the mandibular angular process is completely missing

abnormal Meckel's cartilage morphology ( J:90453 )

• the anterior cartilage derived from the distal extremity of Meckel's cartilage is absent

• anterior region of Meckel's cartilage displays retarded growth and also fails to fuse at E15

• display approximately a 3-fold reduction in proliferation of chondrocytes in the anterior and interior parts of Meckel's cartilage at E13

cellular

impaired cardiac neural crest cell differentiation ( J:90988 )

• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient

abnormal cardiac neural crest cell migration ( J:90988 )

• migration of mutant neural crest cells to the outflow tract is impaired

growth/size/body

enlarged heart ( J:90988 )

• 100% penetrance

abnormal frontal bone squamous part morphology ( J:90453 )

• squamous parts of the frontal bones lack ossification towards the metopic region, resulting in enlarged frontal fontanels in newborns

abnormal mandible morphology ( J:90453 )

abnormal mandibular fossa morphology ( J:90453 )

• the mandibular fossa and its joint cartilage are missing

small mandibular coronoid process ( J:90453 )

• coronoid process of the mandible is rudimentary in size

absent mandibular symphysis ( J:90453 )

• the mental symphysis is not formed resulting in persistently separate mandibular bones

absent temporomandibular joint ( J:90453 )

• the temporomandibular articulation is undetectable

mandible hypoplasia ( J:90453 )

• hypotrophic mandible is apparent as early as E14

short mandible ( J:90453 )

• mandible is about 40% shorter

absent zygomatic bone ( J:90453 )

• completely absent jugal (zygomatic) bone

cleft secondary palate ( J:90453 )

• complete cleft of the secondary palate

abnormal palatal shelf elevation ( J:90453 )

• palatal shelves fail to elevate, either bilaterally or unilaterally, at E14

delayed palatal shelf elevation ( J:90453 )

• in newborns, the unfused palatal shelves are bilaterally elevated, indicating that cleft palate develops as a result of delayed, asynchronous elevation of palatal shelves

shortened head ( J:90453 )

• newborns have a shorter head