Phenotypes Associated with This Genotype

Genotype
MGI:5004709

• Allelic Composition: Ptpn11^tm4.2Bgn/Ptpn11⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

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

Ptpn11^tm4.2Bgn/Ptpn11⁺ mice demonstrate phenotypic abnormalities similar to those in human Leopard syndrome (LS)

mortality/aging

premature death ( J:172033 )

• by 52 weeks, more mice die than wild-type mice

respiratory system

depressed nasal bridge ( J:172033 )

• planar nasal bridge

reproductive system

abnormal reproductive system morphology ( J:172033 )

• mice exhibit abnormal genitals compared with wild-type mice

cardiovascular system

cardiovascular system phenotype ( J:172033 )

N • mice exhibit normal valvular development and no septal defects

increased myocardial fiber size ( J:172033 )

• adult cardiomyocytes exhibit enlarged area and increased cell width compared to in wild-type mice

• however, rapamycin treatment rescues cardiomyocyte size

thick interventricular septum ( J:172033 )

• at 16 weeks

enlarged heart ( J:172033 )

• by 12 weeks

increased heart weight ( J:172033 )

• at 12 and 16 weeks

• however, treatment with rapamycin rescues heart weight

cardiac hypertrophy ( J:172033 )

• with enlarged nuclei, myofiber disarray, and inflammatory cell accumulation in interstitial fiber

heart left ventricle hypertrophy ( J:172033 )

• by 12 weeks

thick ventricular wall ( J:172033 )

• at 16 weeks, mice exhibit thickened left ventricular free wall compared with wild-type mice

cardiac fibrosis ( J:172033 )

• in older mice

dilated cardiomyopathy ( J:172033 )

• by 52 weeks, with increased diastolic dimension and thinning of the posterior walls

• however, treatment with rapamycin normalizes hypertrophic cardiomyopathy

decreased heart ventricle muscle contractility ( J:172033 )

• at 52 weeks

craniofacial

abnormal cranium size ( J:172033 )

• mice exhibit increased skull width-to-length ratio compared with wild-type mice

abnormal facial morphology ( J:172033 )

• with smaller, more slanted eyes and a planar nasal bridge

depressed nasal bridge ( J:172033 )

• planar nasal bridge

growth/size/body

enlarged heart ( J:172033 )

• by 12 weeks

increased heart weight ( J:172033 )

• at 12 and 16 weeks

• however, treatment with rapamycin rescues heart weight

cardiac hypertrophy ( J:172033 )

• with enlarged nuclei, myofiber disarray, and inflammatory cell accumulation in interstitial fiber

heart left ventricle hypertrophy ( J:172033 )

• by 12 weeks

abnormal facial morphology ( J:172033 )

• with smaller, more slanted eyes and a planar nasal bridge

depressed nasal bridge ( J:172033 )

• planar nasal bridge

abnormal chest morphology ( J:172033 )

• skeletal/chest abnormalities

pectus carinatum ( J:172033 )

• pectus carinatum superiorly

pectus excavatum ( J:172033 )

• pectus excavatum inferiorly

decreased body size ( J:172033 )

• by weaning

skeleton

abnormal cranium size ( J:172033 )

• mice exhibit increased skull width-to-length ratio compared with wild-type mice

short femur ( J:172033 )

vision/eye

abnormal eye distance/ position ( J:172033 )

• smaller, more slanted eyes

ocular hypertelorism ( J:172033 )

• with normal inner canthal distance

hearing/vestibular/ear

abnormal organ of Corti morphology ( J:172033 )

• macrophages accumulate in the organ of Corti unlike in wild-type mice

hematopoietic system

hematopoietic system phenotype ( J:172033 )

N • mice exhibit normal hematological parameters

limbs/digits/tail

short femur ( J:172033 )

muscle

increased myocardial fiber size ( J:172033 )

• adult cardiomyocytes exhibit enlarged area and increased cell width compared to in wild-type mice

• however, rapamycin treatment rescues cardiomyocyte size

heart left ventricle hypertrophy ( J:172033 )

• by 12 weeks

dilated cardiomyopathy ( J:172033 )

• by 52 weeks, with increased diastolic dimension and thinning of the posterior walls

• however, treatment with rapamycin normalizes hypertrophic cardiomyopathy

decreased heart ventricle muscle contractility ( J:172033 )

• at 52 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome with multiple lentigines		DOID:14291	OMIM:PS151100	J:172033