Phenotypes Associated with This Genotype

Genotype
MGI:6356633

• Allelic Composition: Rit1^tm1.1Tumg/Rit1⁺
• Genetic Background: B6.Cg-Rit1^tm1.1Tumg

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

mortality/aging

premature death ( J:277548 )

• mice surviving the first 2 days of birth survive until 400 days but then succumb earlier than wild-type mice

lethality during fetal growth through weaning, incomplete penetrance ( J:277548 )

• a reduced Mendelian ratio of heterozygotes is seen at E13.5, E16.5, E18.5, and at birth

postnatal lethality, incomplete penetrance ( J:277548 )

• about 50% of mice die within 2 days after birth

growth/size/body

increased heart weight ( J:277548 )

• mice exhibit heavier heart weight and higher heart weight/body weight ratio at 12 and 26 weeks of age

short snout ( J:277548 )

round head ( J:277548 )

decreased body weight ( J:277548 )

• males exhibit a lower body weight

• females exhibit similar body weight as wild-type except for reduced weight for short periods between 3 and 12 weeks of age and between 52 and 60 weeks of age

decreased body height ( J:277548 )

• adults exhibit a short stature

decreased body length ( J:277548 )

♂ • males exhibit shorter body length at 12 and 26 weeks of age

enlarged spleen ( J:277548 )

cardiovascular system

abnormal heart morphology ( J:277548 )

• heart sections have a higher number of cells, including cardiomyocytes, cardiac fibroblasts, and endothelial cells

• however, cardiomyocyte size is normal

• no cardiovascular abnormalities, including pulmonary stenosis or atrioventricular septal defects, are seen at E16.5

increased heart weight ( J:277548 )

• mice exhibit heavier heart weight and higher heart weight/body weight ratio at 12 and 26 weeks of age

thick ventricular wall ( J:277548 )

• left ventricular wall is thickened

cardiac fibrosis ( J:277548 )

• hearts show a higher level of collagen accumulation at 12 and 26 weeks of age indicating cardiac fibrosis

• beta-adrenergic stimulation by administration of isoproterenol exacerbates cardiac fibrosis to a greater extent than in controls

abnormal cardiovascular system physiology ( J:277548 )

• heart tissue shows a higher proliferation rate at 12 and 26 weeks of age

• hearts show increased expression of S100A4, periostin, and vimentin, indicating that cardiac fibroblasts and myofibroblasts are proliferating or activated

• however, cardiac contractility is comparable to wild-type mice at 28 weeks of age

hemorrhage ( J:277548 )

• 6 of 45 live E16.5 fetuses show severe fetal hydrops and subcutaneous hemorrhage

abnormal heart echocardiography feature ( J:277548 )

• echocardiography shows increased left ventricular end-diastolic dimension and increased posterior wall thickness in diastole

craniofacial

short snout ( J:277548 )

round head ( J:277548 )

digestive/alimentary system

rectal prolapse ( J:277548 )

• 22 of 24 mice exhibit rectal prolapse at 1 year of age

hematopoietic system

enlarged spleen ( J:277548 )

anemia ( J:277548 )

• anemia at 26 weeks of age

• however, no significant increase in the number of white blood cells is seen

homeostasis/metabolism

increased circulating aspartate transaminase level ( J:277548 )

• aspartate transaminase is elevated at 26 weeks of age

• however, other markers of hepatic, renal, and metabolic function are not altered

hydrops fetalis ( J:277548 )

• 6 of 45 live E16.5 fetuses show severe fetal hydrops and subcutaneous hemorrhage

immune system

enlarged spleen ( J:277548 )

reproductive system

reduced female fertility ( J:277548 )

♀

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 8		DOID:0060586	OMIM:615355	J:277548