Phenotypes associated with this allele

• Allele Symbol: Acvr1^tm1.1Vk
• Allele Name: targeted mutation 1.1, Vesa Kaartinen
• Allele ID: MGI:3696672
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Acvr1^tm1.1Vk/Acvr1^tm1.1Vk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3697611
cn2	Acvr1^tm1Vk/Acvr1^tm1.1Vk Tg(Tek-cre)12Flv/0	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6	MGI:3697608
cn3	Acvr1^tm1Vk/Acvr1^tm1.1Vk H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3697607
cn4	Acvr1^tm1Vk/Acvr1^tm1.1Vk Tg(Myh6-cre)2182Mds/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3697609

Genotype
MGI:3697611

hm1

• Allelic Composition: Acvr1^tm1.1Vk/Acvr1^tm1.1Vk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

growth/size/body

decreased embryo size ( J:117234 )

• starting at E7-E7.5, embryos are much smaller

embryo

abnormal gastrulation ( J:117234 )

• at E7-7.5, embryos form empty sacs composed of parietal endoderm as the epiblast is forced into the proamniotic cavity

abnormal mesoderm development ( J:117234 )

• mesoderm formation is initiated but the subsequent development is arrested during the mid-late streak stages

embryonic growth arrest ( J:117234 )

• at the mid-late streak stage

decreased embryo size ( J:117234 )

• starting at E7-E7.5, embryos are much smaller

abnormal embryonic epiblast morphology ( J:117234 )

• the posterior epiblast is forced into the proamniotic cavity by the thicker primitive streak

abnormal primitive streak morphology ( J:117234 )

• thicker primitive streak that forces the posterior epiblast into to the proamniotic cavity

Genotype
MGI:3697608

cn2

• Allelic Composition: Acvr1^tm1Vk/Acvr1^tm1.1Vk; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:103532 )

• only 10% of the expected 25% of mutants are recovered at E14.5

cardiovascular system

abnormal vascular endothelial cell differentiation ( J:103532 )

• endothelial cells (atrioventricular canal tissues) fail to transdifferentiate in vitro

abnormal cardiac epithelial to mesenchymal transition ( J:103532 )

• endothelial cells fail to populate the mesenchyme of the atrioventricular cushions

abnormal heart morphology ( J:103532 )

• at E14.5, surviving embryos show a range of cardiac defects

abnormal atrioventricular cushion morphology ( J:103532 )

• atrioventricular cushions are of variable shape and degree of fusion with one another, or with other septal structures

decreased atrioventricular cushion size ( J:103532 )

• endocardial cushions are smaller at E10; reduction in mesenchymal cell number is particularly evident in the superior cushion

• atrioventricular cushions are of variable size

abnormal atrioventricular valve development ( J:103532 )

• 11 of 17 E14.5 embryos have defective atrioventricular valve development

• outgrowth and formation of atrioventricular leaflets is variable

atrial septal defect ( J:103532 )

• the primary atrial foramen is still patent at E14.5 in some embryos, allowing blood to shunt between right and the left atria

abnormal atrioventricular septum morphology ( J:103532 )

• 11 of 17 E14.5 embryos have defective atrioventricular septation

ventricular septal defect ( J:103532 )

• 15 of 17 E14.5 embryos have a ventricular septal defect of varying severity, where the secondary ventricular foramen has not closed

cardiovascular shunt ( J:103532 )

• the primary atrial foramen is still patent at E14.5 in some embryos, allowing blood to shunt between right and the left atria

cellular

abnormal vascular endothelial cell differentiation ( J:103532 )

• endothelial cells (atrioventricular canal tissues) fail to transdifferentiate in vitro

Genotype
MGI:3697607

cn3

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

mortality/aging

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

• about 40% die in utero (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)

neonatal lethality, complete penetrance ( J:90988 )

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

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

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

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

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

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

Genotype
MGI:3697609

cn4

• Allelic Composition: Acvr1^tm1Vk/Acvr1^tm1.1Vk; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:103532 )

N • mutants are viable and fail to display any detectable altered cardiac phenotype