Phenotypes associated with this allele

• Allele Symbol: Ptpn11^tm1Bgn
• Allele Name: targeted mutation 1, Benjamin G Neel
• Allele ID: MGI:3050284
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptpn11^tm1Bgn/Ptpn11^tm1Bgn	involves: 129S4/SvJae * C57BL/6J	MGI:3050465
ht2	Ptpn11^tm1Bgn/Ptpn11^+	129S6.129S4-Ptpn11^tm1Bgn	MGI:3840263
ht3	Ptpn11^tm1Bgn/Ptpn11^+	B6.129S4-Ptpn11^tm1Bgn	MGI:3840262
ht4	Ptpn11^tm1Bgn/Ptpn11^+	C.129S4-Ptpn11^tm1Bgn	MGI:3840261
ht5	Ptpn11^tm1Bgn/Ptpn11^+	involves: 129S4/SvJae * C57BL/6	MGI:3840260
ht6	Ptpn11^tm1Bgn/Ptpn11^+	involves: 129S4/SvJae * C57BL/6J	MGI:3050469

Genotype
MGI:3050465

hm1

• Allelic Composition: Ptpn11^tm1Bgn/Ptpn11^tm1Bgn
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:91609 )

• homozygous embryos die around E13.5

cardiovascular system

thin myocardium compact layer ( J:91609 )

thin myocardium ( J:91609 )

• the myocardium is markedly thinner compared to wild-type

abnormal heart development ( J:91609 )

• enlarged outflow tract and atrioventricular valve primordia are seen

double outlet right ventricle ( J:91609 )

atrial septal defect ( J:91609 )

• at E13.5 atrial septal defects are seen

atrioventricular septal defect ( J:91609 )

• at E13.5 atrioventricular septal defects are seen

ventricular septal defect ( J:91609 )

• at E13.5 ventricular and atrioventricular septal defects are seen

pericardial effusion ( J:91609 )

• pericardial effusions are seen

hemorrhage ( J:91609 )

• at E13.5 embryos are grossly hemorrhagic

cellular

decreased cardiomyocyte apoptosis ( J:91609 )

• decreased apoptosis is seen in endocardial cushions

increased cell proliferation ( J:91609 )

• increased cellular proliferation is seen in endocardial cushions

homeostasis/metabolism

pericardial effusion ( J:91609 )

• pericardial effusions are seen

hydrops fetalis ( J:91609 )

• at E13.5 embryos are grossly edematous with pericardial and peritoneal effusions and subcutaneous edema

liver/biliary system

small liver ( J:91609 )

• at E13.5 decreased liver size is seen

hepatic necrosis ( J:91609 )

• at E13.5 severe liver necrosis is seen

muscle

thin myocardium compact layer ( J:91609 )

thin myocardium ( J:91609 )

• the myocardium is markedly thinner compared to wild-type

decreased cardiomyocyte apoptosis ( J:91609 )

• decreased apoptosis is seen in endocardial cushions

Genotype
MGI:3840263

ht2

• Allelic Composition: Ptpn11^tm1Bgn/Ptpn11⁺
• Genetic Background: 129S6.129S4-Ptpn11^tm1Bgn

mortality/aging

mortality/aging ( J:147154 )

N • Background Sensitivity: unlike mice on a congenic C57BL/6 background nearly all mice survive

Genotype
MGI:3840262

ht3

• Allelic Composition: Ptpn11^tm1Bgn/Ptpn11⁺
• Genetic Background: B6.129S4-Ptpn11^tm1Bgn

mortality/aging

perinatal lethality, incomplete penetrance ( J:147154 )

• Background Sensitivity: penetrance of lethality is increased compared to mice on a 129S6/SvEv or BALB/c congenic background and to mice on a mixed 129S4/SvJae and C57BL/6 background

• almost all mice die

cardiovascular system

abnormal heart morphology ( J:147154 )

• all mice show severe cardiac defects

Genotype
MGI:3840261

ht4

• Allelic Composition: Ptpn11^tm1Bgn/Ptpn11⁺
• Genetic Background: C.129S4-Ptpn11^tm1Bgn

mortality/aging

perinatal lethality, incomplete penetrance ( J:147154 )

• about 50% of mice die either in late gestation or perinatally

• Background Sensitivity: penetrance of lethality is decreased compared to mice on a congenic C57BL/6 background

Genotype
MGI:3840260

ht5

• Allelic Composition: Ptpn11^tm1Bgn/Ptpn11⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:147154 )

• about 50% of mice die either in late gestation or perinatally

• Background Sensitivity: penetrance of lethality is decreased compared to mice on a congenic C57BL/6 background

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:147154 )

• from 24 - 48 hours in culture endocardial cushions from E9.5 embryos give rise to more mesenchymal cells compared to wild-type controls

• expression analysis indicates that enhanced production of mesenchymal cells is due to a prolongation of the normal interval during which EMT occurs

growth/size/body

decreased body weight ( J:147154 )

decreased body length ( J:147154 )

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:147154 )

• increase in the number of CFU-GM in the absence of cytokines compared to wild-type controls

vision/eye

increased inner canthal distance ( J:147154 )

• increased inner canthal distance

Genotype
MGI:3050469

ht6

• Allelic Composition: Ptpn11^tm1Bgn/Ptpn11⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

perinatal lethality, incomplete penetrance ( J:91609 )

• at E18.5 some heterozygous embryos are dead and about 50% fewer than expected heterozygotes are found at weaning

cardiovascular system

abnormal heart development ( J:91609 )

• enlarged atrioventricular valve primordia are seen in about 50% of heterozygotes (severely affected mutants)

double outlet right ventricle ( J:91609 )

• double outlet right ventricle is seen in about 50% of heterozygotes (severely affected mutants)

enlarged mitral valve ( J:91609 )

• enlarged mitral valves are seen in about 50% of heterozygotes (not severely affected) at E13.5 but not at E18.5

ventricular septal defect ( J:91609 )

• at E13.5 ventricular septal defects are seen in about 50% of heterozygotes (severely affected mutants)

cellular

decreased cardiomyocyte apoptosis ( J:91609 )

• decreased apoptosis is seen in endocardial cushions from some heterozygous mutants

increased cell proliferation ( J:91609 )

• increased cellular proliferation is seen in endocardial cushions from some heterozygous mutants

craniofacial

small cranium ( J:91609 )

• consistent with the decreased body size the skull is smaller than normal however width is not different from wild-type resulting in a greater length/width ratio

broad snout ( J:91609 )

• a wider and blunter snout shape is seen

flattened snout ( J:91609 )

• a wider and blunter snout shape is seen

growth/size/body

broad snout ( J:91609 )

• a wider and blunter snout shape is seen

flattened snout ( J:91609 )

• a wider and blunter snout shape is seen

decreased body weight ( J:91609 )

• a significant reduction in body weight and length is seen without altering overall body proportions

decreased body length ( J:91609 )

• a significant reduction in body weight and length is seen without altering overall body proportions

enlarged spleen ( J:91609 )

• older heterozygotes develop splenomegaly with mild myeloid and erythroid hyperplasia

hematopoietic system

enlarged spleen ( J:91609 )

• older heterozygotes develop splenomegaly with mild myeloid and erythroid hyperplasia

myeloid hyperplasia ( J:91609 )

• mild myeloid hyperplasia is seen in the bone marrow of older heterozygotes

increased leukocyte cell number ( J:91609 )

• by 5 months heterozygotes develop mild leukocytosis with normal hematocrit and platelet counts

increased neutrophil cell number ( J:91609 )

increased lymphocyte cell number ( J:91609 )

immune system

enlarged spleen ( J:91609 )

• older heterozygotes develop splenomegaly with mild myeloid and erythroid hyperplasia

myeloid hyperplasia ( J:91609 )

• mild myeloid hyperplasia is seen in the bone marrow of older heterozygotes

increased leukocyte cell number ( J:91609 )

• by 5 months heterozygotes develop mild leukocytosis with normal hematocrit and platelet counts

increased neutrophil cell number ( J:91609 )

increased lymphocyte cell number ( J:91609 )

liver/biliary system

hepatic necrosis ( J:91609 )

• at E13.5 some heterozygotes display mild liver damage

skeleton

small cranium ( J:91609 )

• consistent with the decreased body size the skull is smaller than normal however width is not different from wild-type resulting in a greater length/width ratio

muscle

decreased cardiomyocyte apoptosis ( J:91609 )

• decreased apoptosis is seen in endocardial cushions from some heterozygous mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 1		DOID:0060578	OMIM:163950	J:91609