Phenotypes Associated with This Genotype

Genotype
MGI:5003451

• Allelic Composition: Raf1^tm1.1Bgn/Raf1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCr

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

Raf1^tm1.1Bgn/Raf1⁺ mice show multiple Noonan syndrome phenotypes including short stature, facial dysmorphia and splenomegaly

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:172034 )

• following transverse aortic constriction

cardiovascular system

cardiovascular system phenotype ( J:172034 )

N • fetal cardiomyocyte proliferation and valve development are normal

increased myocardial fiber size ( J:172034 )

• at 8 weeks of age

• however, treatment with a MEK inhibitor rescues cardiomyocyte enlargement

increased heart right atrium size ( J:172034 )

• following transverse aortic constriction

thick interventricular septum ( J:172034 )

increased heart weight ( J:172034 )

• as early as 2 weeks after birth

• following transverse aortic constriction

cardiac hypertrophy ( J:172034 )

• however, treatment with MEK inhibitor rescues cardiac hypertrophy

abnormal heart left ventricle morphology ( J:189143 )

• increased left ventricular diastolic posterior wall thickness

• increased left ventricular internal end-diastolic dimension

increased heart ventricle size ( J:172034 )

• following transverse aortic constriction

increased heart left ventricle size ( J:172034 )

• at 4 months, mice exhibit increased left ventricle internal end-diastolic dimension (LVIDd) compared with wild-type mice

• however, LVIDd is normal at 2 months of age and left ventricle internal end-systolic dimension is normal

thick ventricular wall ( J:172034 )

• mice exhibit increased ventricular wall thickness compared with wild-type mice

• at 2 and 4 months of age, left ventricular diastolic posterior wall thickness is increased compared to in wild-type mice

cardiac fibrosis ( J:172034 )

• following transverse aortic constriction, mice exhibit severe cardiac interstitial fibrosis and perivascular fibrosis compared with wild-type mice

cardiac interstitial fibrosis ( J:172034 )

• following transverse aortic constriction

abnormal cardiovascular system physiology ( J:172034 )

• mice exhibit abnormal cardiac function compared with wild-type mice

• however, treatment with a MEK inhibitor normalizes cardiac function

dilated cardiomyopathy ( J:172034 )

• as early as 2 weeks after birth

increased cardiac output ( J:172034 , J:189143 )

• at 2 and 4 months (J:172034)

• increased (J:189143)

increased cardiac stroke volume ( J:172034 , J:189143 )

• at 2 and 4 months, mice exhibit increased stroke volume compared with wild-type mice (J:172034)

• following transverse aortic constriction, mice exhibit increased stroke volume compared with wild-type mice (J:172034)

decreased cardiac muscle contractility ( J:172034 )

• following transverse aortic constriction

increased cardiac muscle contractility ( J:172034 , J:189143 )

• at 2 and 4 months, mice exhibit increased ejection fraction and fractional shortening compared with wild-type mice (J:172034)

• however, cardiac relaxation is normal (J:172034)

• increased fractional shortening and ejection fraction (J:189143)

abnormal heart left ventricle pressure ( J:172034 )

• at 4 months, mice exhibit decreased left ventricle pressure compared with wild-type mice

increased left ventricle systolic pressure ( J:172034 )

• following transverse aortic constriction

increased response of heart to induced stress ( J:172034 )

• following transverse aortic constriction, mice exhibit increased lethality, ventricular and left atrial enlargement, increased heart weight, severe interstitial fibrosis, perivascular fibrosis, deteriorating cardiac function (stroke volume and fractional shortening), decreased cardiac contractility, infarct, and fatal, functional decompensation in some mice compared with wild-type mice

immune system

enlarged spleen ( J:172034 )

• increasing in severity with age

increased leukocyte cell number ( J:172034 )

• at 1 year of age

increased neutrophil cell number ( J:172034 )

• at 1 year of age

increased monocyte cell number ( J:172034 )

• at 1 year of age

craniofacial

decreased cranium height ( J:172034 )

increased cranium width ( J:172034 )

abnormal facial morphology ( J:172034 )

• mice exhibit facial dysmorphia compared with wild-type mice

• however, treatment with a MEK inhibitory rescues facial dysmorphia

flattened snout ( J:172034 )

• blunt snout

growth/size/body

increased heart weight ( J:172034 )

• as early as 2 weeks after birth

• following transverse aortic constriction

cardiac hypertrophy ( J:172034 )

• however, treatment with MEK inhibitor rescues cardiac hypertrophy

abnormal facial morphology ( J:172034 )

• mice exhibit facial dysmorphia compared with wild-type mice

• however, treatment with a MEK inhibitory rescues facial dysmorphia

flattened snout ( J:172034 )

• blunt snout

decreased body size ( J:172034 )

• at weaning

decreased body weight ( J:172034 )

• however, mice treated with a MEK inhibitor normalizes weight

decreased body length ( J:172034 )

• however, mice treated with a MEK inhibitor normalizes length

enlarged spleen ( J:172034 )

• increasing in severity with age

homeostasis/metabolism

increased response of heart to induced stress ( J:172034 )

• following transverse aortic constriction, mice exhibit increased lethality, ventricular and left atrial enlargement, increased heart weight, severe interstitial fibrosis, perivascular fibrosis, deteriorating cardiac function (stroke volume and fractional shortening), decreased cardiac contractility, infarct, and fatal, functional decompensation in some mice compared with wild-type mice

muscle

increased myocardial fiber size ( J:172034 )

• at 8 weeks of age

• however, treatment with a MEK inhibitor rescues cardiomyocyte enlargement

dilated cardiomyopathy ( J:172034 )

• as early as 2 weeks after birth

decreased cardiac muscle contractility ( J:172034 )

• following transverse aortic constriction

increased cardiac muscle contractility ( J:172034 , J:189143 )

• at 2 and 4 months, mice exhibit increased ejection fraction and fractional shortening compared with wild-type mice (J:172034)

• however, cardiac relaxation is normal (J:172034)

• increased fractional shortening and ejection fraction (J:189143)

skeleton

decreased cranium height ( J:172034 )

increased cranium width ( J:172034 )

vision/eye

ocular hypertelorism ( J:172034 )

hematopoietic system

enlarged spleen ( J:172034 )

• increasing in severity with age

abnormal common myeloid progenitor cell morphology ( J:172034 )

• myeloid progenitors are expanded compared to in wild-type mice

increased leukocyte cell number ( J:172034 )

• at 1 year of age

increased neutrophil cell number ( J:172034 )

• at 1 year of age

increased monocyte cell number ( J:172034 )

• at 1 year of age

cellular

cardiac interstitial fibrosis ( J:172034 )

• following transverse aortic constriction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 5		DOID:0060583	OMIM:611553	J:172034