Phenotypes Associated with This Genotype

Genotype
MGI:5902221

• Allelic Composition: Braf^tm1Tumg/Braf⁺; Tg(CAG-cre)2Osb/0
• Genetic Background: involves: C57BL * C57BL/6J * DBA

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

cardiovascular system

abnormal heart morphology ( J:216228 )

• 93% of hearts at E16.5 show various defects

abnormal coronary artery morphology ( J:216228 )

• 3 of 14 embryos show hypoplasia of the coronary arteries

abnormal myocardial trabeculae morphology ( J:216228 )

• E14.5 hearts show an increase in density of trabeculae (hypertrabeculation)

• 4 of 14 embryos exhibit a thickened trabecular layer and thinned compact layer in the left, right, or combined myocardium

thin myocardium compact layer ( J:216228 )

• 4 of 14 embryos exhibit a thickened trabecular layer and thinned compact layer in the left, right, or combined myocardium

abnormal heart development ( J:216228 )

• hearts exhibit enhanced cell proliferation

• at E13.5, the interventricular septum and myocardium show enhanced cell proliferation

• at E16.5, the pulmonary valves and the interventricular septum in fetuses with ventricular septal defect, show enhanced cell proliferation

abnormal atrioventricular cushion morphology ( J:216228 )

• 2 of 14 embryos exhibit abnormal endocardial cushion

mitral valve hypertrophy ( J:216228 )

• 9 of 14 embryos show hypertrophy of mitral valves

• co-treatment with PD0325901 and an inhibitor of histone H3K27 demethylase UTX, GSK-J4, ameliorates enlarged mitral valves, however, no difference in the frequency of heart defects is seen

tricuspid valve hypertrophy ( J:216228 )

• 8 of 14 embryos show hypertrophy of tricuspid valves

• co-treatment with PD0325901 and an inhibitor of histone H3K27 demethylase UTX, GSK-J4, ameliorates enlarged tricuspid valves, however, no difference in the frequency of heart defects is seen

thick tricuspid valve ( J:216228 )

• ventricular radius and the thickness of the tricuspid valves are higher

ventricular septal defect ( J:216228 )

• 2 of 14 embryos exhibit ventricular septal defect

enlarged heart ( J:216228 )

• increase in heart size at E16.5

abnormal pulmonary valve cusp morphology ( J:216228 )

• hypertrophy in pulmonary valve leaflets is prominent, plugging the entire space of the pulmonary valve ring

enlarged pulmonary valve ( J:216228 )

• E12.5 hearts show an enlarged pulmonary valve

• co-treatment with PD0325901 and an inhibitor of histone H3K27 demethylase UTX, GSK-J4, ameliorates enlarged pulmonary valves, however, no difference in the frequency of heart defects is seen

pulmonary valve hypertrophy ( J:216228 )

• 7 of 14 embryos show hypertrophy of pulmonary valves

thick pulmonary valve ( J:216228 )

• ventricular radius and the thickness of the pulmonary valves are higher

abnormal epicardium morphology ( J:216228 )

• 2 of 14 embryos show epicardial blisters

hemorrhage ( J:216228 )

• at E16.5, about 9.8% of embryos are hemorrhagic and edematous

pulmonary alveolar hemorrhage ( J:216228 )

• about 11.1% of fetuses at E18.5 and E19.5 show alveolar hemorrhage

• however, lungs are able to inflate

immune system

abnormal lymph organ development ( J:216228 )

• cavities such as the jugular lymphatic sacs from E12.5 to E14.5 are observed unlike in wild-type where they are hardly observed at this time, suggesting defective lymphatic development from the cardinal vein

• marker analysis indicates that embryos show defective lymphatic development from the cardinal vein, leading to distended and blood-filled jugular lymphatic sacs at E12.5 and E16.5, dilated lymphatic vessels and edema

craniofacial

mandible hypoplasia ( J:216228 )

• 5.1% of embryos show mandibular hypoplasia and kyphosis

homeostasis/metabolism

cyanosis ( J:216228 )

• embryos delivered by cesarean section at E18.5 and E19.5 are pale, without movement and gasp for breath with cyanotic appearance and death within a few hours

edema ( J:216228 )

• at E16.5, about 9.8% of embryos are hemorrhagic and edematous

liver/biliary system

small liver ( J:216228 )

decreased liver weight ( J:216228 )

• decrease in liver weight is seen already at E16.5

hepatic necrosis ( J:216228 )

• 88% of E18.5 fetuses show severe peripheral liver necrosis with decreased liver size and liver weight

mortality/aging

neonatal lethality, complete penetrance ( J:216228 )

• no surviving mice are seen at weaning and survival rate of embryos drops after E16.5 indicating embryonic and neonatal lethality

lethality throughout fetal growth and development, incomplete penetrance ( J:216228 )

• no surviving mice are seen at weaning and survival rate of embryos drops after E16.5 indicating embryonic and neonatal lethality

• treatment of pregnant mice with the MEK inhibitor PD0325901 partly rescues embryonic lethality and combined treatment with PD0325901 and a histone demethylase inhibitor further increases survival rate

muscle

abnormal myocardial trabeculae morphology ( J:216228 )

• E14.5 hearts show an increase in density of trabeculae (hypertrabeculation)

• 4 of 14 embryos exhibit a thickened trabecular layer and thinned compact layer in the left, right, or combined myocardium

thin myocardium compact layer ( J:216228 )

• 4 of 14 embryos exhibit a thickened trabecular layer and thinned compact layer in the left, right, or combined myocardium

respiratory system

pulmonary alveolar hemorrhage ( J:216228 )

• about 11.1% of fetuses at E18.5 and E19.5 show alveolar hemorrhage

• however, lungs are able to inflate

skeleton

mandible hypoplasia ( J:216228 )

• 5.1% of embryos show mandibular hypoplasia and kyphosis

kyphosis ( J:216228 )

• 5.1% of embryos show mandibular hypoplasia and kyphosis

growth/size/body

enlarged heart ( J:216228 )

• increase in heart size at E16.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cardiofaciocutaneous syndrome		DOID:0060233	OMIM:PS115150	J:216228