Phenotypes Associated with This Genotype

Genotype
MGI:5000309

• Allelic Composition: Sos1^tm1.2Rak/Sos1^tm1.2Rak
• Genetic Background: involves: 129S/Sv * C57BL/6 * FVB/N * SJL

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

Cardiac defects in Sos1^tm1.2Rak/Sos1^tm1.2Rak and Sos1^tm1.2Rak/Sos1⁺ mice

mortality/aging

premature death ( J:171873 )

• mice that survive birth die exhibit premature lethality

lethality throughout fetal growth and development, incomplete penetrance ( J:171873 )

• fewer than expected mice are present at E15.5

embryonic lethality during organogenesis, incomplete penetrance ( J:171873 )

• fewer than expected mice are present at E10.5 and E13.5

• however, treatment with the MEK inhibitor PD0325901 improves embryonic lethality

cardiovascular system

abnormal heart morphology ( J:171873 )

• mice exhibit adipocyte infiltration in the ventricular myocardium and the surrounding blood vessels unlike in wild-type mice

• however, mice treated with PD0325901 exhibit no anatomical heart abnormalities

myocardial fiber degeneration ( J:171873 )

heart right ventricle hypertrophy ( J:171873 )

• at E15.5

ostium secundum atrial septal defect ( J:171873 )

• at E15.5

thick interventricular septum ( J:171873 )

ventricular septal defect ( J:171873 )

• at E15.5

thick aortic valve cusps ( J:171873 )

• at E15.5 and at 3 months

aortic valve stenosis ( J:171873 )

• at E15.5 and at 3 months due to thickened leaflets

pericardial effusion ( J:171873 )

• at E15.5

cardiac fibrosis ( J:171873 )

• at 3 months, mice exhibit epicardial and myocardial fibrosis unlike wild-type mice

abnormal cardiovascular system physiology ( J:171873 )

• at E15.5, mice exhibit increased proliferation and decreased apoptosis in the interventricular septal and aortic valve tissues compared with wild-type mice

hemorrhage ( J:171873 )

• mice exhibit subcutaneous hemorrhage unlike wild-type mice

abnormal fetal cardiomyocyte proliferation ( J:171873 )

• at E15.5, mice exhibit increased proliferation and decreased apoptosis in the interventricular septal and aortic valve tissues compared with wild-type mice

growth/size/body

heart right ventricle hypertrophy ( J:171873 )

• at E15.5

decreased body size ( J:171873 )

decreased body weight ( J:171873 )

• however, treatment with PD0325901 improves body weight

decreased body length ( J:171873 )

homeostasis/metabolism

pericardial effusion ( J:171873 )

• at E15.5

skin edema ( J:171873 )

craniofacial

abnormal craniofacial morphology ( J:171873 )

• at 3 months, mice exhibit a tend towards triangular faces with blunter snouts because of depression of the anterior frontal bone compared with wild-type mice

• however, treatment with PD0325901 improves facial dysmorphia

decreased cranium height ( J:171873 )

• at 3 months

abnormal frontal bone morphology ( J:171873 )

• at 3 months, mice exhibit depression of the anterior frontal bone compared with wild-type mice

integument

skin edema ( J:171873 )

muscle

myocardial fiber degeneration ( J:171873 )

heart right ventricle hypertrophy ( J:171873 )

• at E15.5

abnormal fetal cardiomyocyte proliferation ( J:171873 )

• at E15.5, mice exhibit increased proliferation and decreased apoptosis in the interventricular septal and aortic valve tissues compared with wild-type mice

skeleton

decreased cranium height ( J:171873 )

• at 3 months

abnormal frontal bone morphology ( J:171873 )

• at 3 months, mice exhibit depression of the anterior frontal bone compared with wild-type mice

vision/eye

ocular hypertelorism ( J:171873 )

• at 3 months

cellular

abnormal fetal cardiomyocyte proliferation ( J:171873 )

• at E15.5, mice exhibit increased proliferation and decreased apoptosis in the interventricular septal and aortic valve tissues compared with wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 4		DOID:0060582	OMIM:610733	J:171873