Phenotypes associated with this allele

• Allele Symbol: Ptpn11^tm4.2Bgn
• Allele Name: targeted mutation 4.2, Benjamin G Neel
• Allele ID: MGI:5004658
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Ptpn11^tm4.2Bgn/Ptpn11^+	B6.129S6-Ptpn11^tm4.2Bgn	MGI:6507961
ht2	Ptpn11^tm4.2Bgn/Ptpn11^+	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5004709
cx3	Mpzl1^em1Ambt/Mpzl1^em1Ambt Ptpn11^tm4.2Bgn/Ptpn11^tm4.2Bgn	B6.Cg-Mpzl1^em1Ambt Ptpn11^tm4.2Bgn	MGI:6507959

Genotype
MGI:6507961

ht1

• Allelic Composition: Ptpn11^tm4.2Bgn/Ptpn11⁺
• Genetic Background: B6.129S6-Ptpn11^tm4.2Bgn

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

cardiovascular system

abnormal interventricular septum morphology ( J:301775 )

• increased interventricular septum wall (IVS) thickness

increased heart weight ( J:301775 )

• increased heart weight and HW to body weight ratio at age 16 weeks

thick ventricular wall ( J:301775 )

• increased left ventricular posterior wall (LVPW) thickness at age 16 weeks

cardiac fibrosis ( J:301775 )

growth/size/body

increased heart weight ( J:301775 )

• increased heart weight and HW to body weight ratio at age 16 weeks

Genotype
MGI:5004709

ht2

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

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

Genotype
MGI:6507959

cx3

• Allelic Composition: Mpzl1^em1Ambt/Mpzl1^em1Ambt; Ptpn11^tm4.2Bgn/Ptpn11^tm4.2Bgn
• Genetic Background: B6.Cg-Mpzl1^em1Ambt Ptpn11^tm4.2Bgn

cardiovascular system

cardiovascular system phenotype ( J:301775 )

N • normal heart weight (HW) and HW to body weight (BW) and tibia length (TL) ratios and interventricular septum wall (IVS) and left ventricular posterior wall (LVPW) thickness at age 16 weeks

N • no myocardial fibrosis

growth/size/body

growth/size/body region phenotype ( J:301775 )

N • normal heart weight (HW) and HW to body weight (BW) and tibia length (TL) ratios at age 16 weeks

slow postnatal weight gain ( J:301775 )