Phenotypes Associated with This Genotype

Genotype
MGI:3623395

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CBA/J

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

mortality/aging

postnatal lethality, complete penetrance ( J:104325 )

• lethality in the immediate postnatal period

cardiovascular system

abnormal dorsal aorta morphology ( J:104325 )

• the dorsal aorta is supplied soley via the ductus arteriosus

abnormal fourth pharyngeal arch artery morphology ( J:104325 )

• all exhibit inappropriate regression of the left 4th arch artery and 30% of the right arch artery

• inappropriate apoptosis in the 4th arch artery, however normal neural crest cell migration, smooth muscle differentiation and pharyngeal endodermal organ development

abnormal aortic arch morphology ( J:104325 )

retroesophageal right subclavian artery ( J:104325 )

• 5/17 have a right subclavian artery that originates retroesophageally from the dorsal aorta

interrupted aortic arch, type b ( J:104325 )

• E12.5 or older embryos have an interruption of the aortic arch between the left carotid artery and the left subclavian artery (IAA type B)

persistent truncus arteriosus ( J:104325 )

• all E12.5 or older embryos exhibit persistent truncus arteriosus, specifically subtype PTA-A4, resulting from a failure in the formation of the aorticopulmonary (A/P) septum

• the ascending aorta branches into the carotid arteries but does not connect to the dorsal aorta, and the dorsal aorta is supplied soley via the ductus arteriosus

ventricular septal defect ( J:104325 )

• ventricular septum defect

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:104325 )

• all exhibit inappropriate regression of the left 4th arch artery and 30% of the right arch artery

• inappropriate apoptosis in the 4th arch artery, however normal neural crest cell migration, smooth muscle differentiation and pharyngeal endodermal organ development

abnormal cranium morphology ( J:86042 )

• show severe skull defects at birth

small cranium ( J:86042 )

• skull is about 25% smaller than in wild-type

abnormal neurocranium morphology ( J:86042 )

• calvaria development is impaired

absent frontal bone ( J:86042 )

• missing at birth

abnormal parietal bone morphology ( J:86042 )

• induction of parietal bone development fails to occur at E16.5

• severely retarded parietal bone at birth

abnormal mandible morphology ( J:86042 )

absent mandibular angle ( J:86042 )

• at birth shows a missing mandibular angle

small mandibular condyloid process ( J:86042 )

• at birth shows a reduction in the condyle

small mandibular coronoid process ( J:86042 )

• at birth shows a reduction in the coronoid process

small mandible ( J:86042 )

• mandible is smaller at birth

small maxilla ( J:86042 )

• maxilla is smaller at birth

abnormal palate morphology ( J:86042 )

• complete failure of secondary palate fusion at E14.5

abnormal palatal mesenchymal cell proliferation ( J:86042 )

• significant reduction in the cell proliferation rate within the cranial neural crest-derived palatal mesenchyme

palatal shelves fail to meet at midline ( J:86042 )

• shelves do not meet at the midline and fuse, but E13.5 mutant shelves cultured in vitro are able to fuse when placed in proximity to each other, suggesting that failure of palatal mesenchymal cell proliferation and extension to the midline is the cause of cleft palate in mutant mice

palatal shelf hypoplasia ( J:86042 )

• decrease in cellular density in the elevated palatal shelf mesenchyme

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

cleft secondary palate ( J:86042 )

• at birth, 100% of newborns have complete cleft secondary palate

nervous system

abnormal brain dura mater morphology ( J:86042 )

• dura mater development is severely impaired at E14.5, with embryos showing a single cell layer that is poorly developed

skeleton

abnormal cranium morphology ( J:86042 )

• show severe skull defects at birth

small cranium ( J:86042 )

• skull is about 25% smaller than in wild-type

abnormal neurocranium morphology ( J:86042 )

• calvaria development is impaired

absent frontal bone ( J:86042 )

• missing at birth

abnormal parietal bone morphology ( J:86042 )

• induction of parietal bone development fails to occur at E16.5

• severely retarded parietal bone at birth

abnormal mandible morphology ( J:86042 )

absent mandibular angle ( J:86042 )

• at birth shows a missing mandibular angle

small mandibular condyloid process ( J:86042 )

• at birth shows a reduction in the condyle

small mandibular coronoid process ( J:86042 )

• at birth shows a reduction in the coronoid process

small mandible ( J:86042 )

• mandible is smaller at birth

small maxilla ( J:86042 )

• maxilla is smaller at birth

embryo

abnormal fourth pharyngeal arch artery morphology ( J:104325 )

• all exhibit inappropriate regression of the left 4th arch artery and 30% of the right arch artery

• inappropriate apoptosis in the 4th arch artery, however normal neural crest cell migration, smooth muscle differentiation and pharyngeal endodermal organ development

decreased cranial neural crest cell proliferation ( J:86042 )

• cranial neural crest (CNC) cell proliferation activity is severely impaired at E14.5, however no defect in CNC migration

digestive/alimentary system

abnormal palate morphology ( J:86042 )

• complete failure of secondary palate fusion at E14.5

abnormal palatal mesenchymal cell proliferation ( J:86042 )

• significant reduction in the cell proliferation rate within the cranial neural crest-derived palatal mesenchyme

palatal shelves fail to meet at midline ( J:86042 )

• shelves do not meet at the midline and fuse, but E13.5 mutant shelves cultured in vitro are able to fuse when placed in proximity to each other, suggesting that failure of palatal mesenchymal cell proliferation and extension to the midline is the cause of cleft palate in mutant mice

palatal shelf hypoplasia ( J:86042 )

• decrease in cellular density in the elevated palatal shelf mesenchyme

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

cleft secondary palate ( J:86042 )

• at birth, 100% of newborns have complete cleft secondary palate

cellular

decreased cranial neural crest cell proliferation ( J:86042 )

• cranial neural crest (CNC) cell proliferation activity is severely impaired at E14.5, however no defect in CNC migration

muscle

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

growth/size/body

absent frontal bone ( J:86042 )

• missing at birth

abnormal mandible morphology ( J:86042 )

absent mandibular angle ( J:86042 )

• at birth shows a missing mandibular angle

small mandibular condyloid process ( J:86042 )

• at birth shows a reduction in the condyle

small mandibular coronoid process ( J:86042 )

• at birth shows a reduction in the coronoid process

small mandible ( J:86042 )

• mandible is smaller at birth

small maxilla ( J:86042 )

• maxilla is smaller at birth

abnormal palate morphology ( J:86042 )

• complete failure of secondary palate fusion at E14.5

abnormal palatal mesenchymal cell proliferation ( J:86042 )

• significant reduction in the cell proliferation rate within the cranial neural crest-derived palatal mesenchyme

palatal shelves fail to meet at midline ( J:86042 )

• shelves do not meet at the midline and fuse, but E13.5 mutant shelves cultured in vitro are able to fuse when placed in proximity to each other, suggesting that failure of palatal mesenchymal cell proliferation and extension to the midline is the cause of cleft palate in mutant mice

palatal shelf hypoplasia ( J:86042 )

• decrease in cellular density in the elevated palatal shelf mesenchyme

abnormal soft palate muscle morphology ( J:208431 )

• muscle abnormalities in the soft palate

cleft secondary palate ( J:86042 )

• at birth, 100% of newborns have complete cleft secondary palate