Phenotypes associated with this allele

• Allele Symbol: Ptpn11^tm1Paw
• Allele Name: targeted mutation 1, Anthony Pawson
• Allele ID: MGI:2176524
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptpn11^tm1Paw/Ptpn11^tm1Paw	involves: 129S1/Sv * 129X1/SvJ	MGI:3621559
hm2	Ptpn11^tm1Paw/Ptpn11^tm1Paw	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2176525
cx3	Egfr^wa2/Egfr^wa2 Ptpn11^tm1Paw/Ptpn11^+	involves: 129S1/Sv * 129X1/SvJ * B6EiC3Sn a/A-Egfr^wa2 Wnt3a^vt * C57BL/6	MGI:2176569

Genotype
MGI:3621559

hm1

• Allelic Composition: Ptpn11^tm1Paw/Ptpn11^tm1Paw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

cellular

polyploidy ( J:106624 )

• cultured trophoblast stem cells exhibit an increase in ploidy under differentiating conditions

abnormal cell death ( J:106624 )

• null trophoblast stem cells die rapidly in culture

decreased cell proliferation ( J:106624 )

• mutation causes decreased trophoblast stem cell proliferation and colony formation in culture

Genotype
MGI:2176525

hm2

• Allelic Composition: Ptpn11^tm1Paw/Ptpn11^tm1Paw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:43740 )

• die around E10-11

growth/size/body

embryonic growth retardation ( J:43740 )

• E8.5 embryos are small and appear similar in size to wild-type E7.5 embryos

embryo

abnormal gastrulation ( J:43740 )

failure of initiation of embryo turning ( J:43740 )

• do not initiate the process of turning

abnormal rostral-caudal axis patterning ( J:43740 )

• about 30% fail to develop an A-P axis or any recognizable embryonic structures

• E8.5 embryos fail to elongate posteriorly

caudal body truncation ( J:43740 )

• some E9.5 embryos develop a defined A-P axis, however all exhibit varying degrees of posterior truncations

embryonic growth arrest ( J:43740 )

• 30% arrest development prior to the formation of recognizable structures

embryonic growth retardation ( J:43740 )

• E8.5 embryos are small and appear similar in size to wild-type E7.5 embryos

abnormal axial mesoderm morphology ( J:43740 )

• development of axial mesodermal structures is severely affected

abnormal neural tube morphology ( J:43740 )

• variable neural tube defects

abnormal embryonic neuroepithelium morphology ( J:43740 )

• disorganized neuroectoderm

open neural tube ( J:43740 )

• headfolds do not fuse at the midline at E9

kinked neural tube ( J:43740 )

• severely affected mutants have a kinked neural tube

abnormal notochord morphology ( J:43740 )

• E8.5 embryos do not develop a notochord

• abnormal notochord at E9.5; some have multiple, split, or kinked notochords

incomplete somite formation ( J:43740 )

• poorly developed somites, with some mutants able to form somites whereas others fail to make any recognizable somites

abnormal allantois morphology ( J:43740 )

• allantois does not develop properly and does not connect to the placenta

abnormal visceral yolk sac morphology ( J:43740 )

• yolk sac is abnormally thin and wrinkled

abnormal vitelline vascular remodeling ( J:43740 )

• yolk sac blood vessels fail to re-organize into a highly vascularized network at E9.5 and remain in a honeycombed pattern seen in E8.5 wild-type embryos, however vasculogenesis and production of the capillary plexus occurs normally

• thick-walled blood vessels do not form in yolk sacs

cardiovascular system

abnormal heart development ( J:43740 )

• heart forms abnormally

nervous system

abnormal neural tube morphology ( J:43740 )

• variable neural tube defects

abnormal embryonic neuroepithelium morphology ( J:43740 )

• disorganized neuroectoderm

open neural tube ( J:43740 )

• headfolds do not fuse at the midline at E9

kinked neural tube ( J:43740 )

• severely affected mutants have a kinked neural tube

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Noonan syndrome 1	DOID:0060578	OMIM:163950	J:43740

Genotype
MGI:2176569

cx3

• Allelic Composition: Egfr^wa2/Egfr^wa2; Ptpn11^tm1Paw/Ptpn11⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * B6EiC3Sn a/A-Egfr^wa2 Wnt3a^vt * C57BL/6

Defects in the skin, lung and intestine of Egfr^wa2/Egfr^wa2 Ptpn11^tm1Paw/⁺ mice

mortality/aging

postnatal lethality, incomplete penetrance ( J:75413 )

• only 30% survive to weaning, with most dying within 7-10 days after birth

growth/size/body

cachexia ( J:75413 )

• exhibit progressive wasting

postnatal growth retardation ( J:75413 )

muscle

intestinal hypoperistalsis ( J:75413 )

• lumen of stomach and small and large bowels are filled with desquamated epithelial cells, suggesting lack of peristalsis

abnormal muscle morphology ( J:75413 )

• decrease in the size of subcutaneous muscle tissue

respiratory system

abnormal lung development ( J:75413 )

• lungs are immaturely developed with poorly inflated areas

atelectasis ( J:75413 )

thick pulmonary interalveolar septum ( J:75413 )

• increase in thickness and cell masses of the alveolar septae

abnormal breathing pattern ( J:75413 )

• display breathing difficulties

vision/eye

eyelids open at birth ( J:75413 )

adipose tissue

decreased subcutaneous adipose tissue amount ( J:75413 )

• decrease in the size of subcutaneous fat tissue

digestive/alimentary system

abnormal intestine morphology ( J:75413 )

• the muscle layer of the bowel is poorly organized and is decreased in thickness

intestinal hypoperistalsis ( J:75413 )

• lumen of stomach and small and large bowels are filled with desquamated epithelial cells, suggesting lack of peristalsis

integument

decreased subcutaneous adipose tissue amount ( J:75413 )

• decrease in the size of subcutaneous fat tissue

abnormal hair growth ( J:75413 )

• little hair outgrowth

waved hair ( J:75413 )

abnormal hair follicle morphology ( J:75413 )

abnormal hair follicle development ( J:75413 )

• poorly developed hair follicles

abnormal hair follicle orientation ( J:75413 )

• hair follicles are disordered

decreased hair follicle number ( J:75413 )

• skin contains no or few disorganized hair follicles

epidermal atrophy ( J:75413 )

• hypotrophy in the epidermis

thin epidermis ( J:75413 )

dry skin ( J:75413 )

• skin gradually becomes dry and flaky

flaky skin ( J:75413 )

• skin gradually becomes dry and flaky

abnormal skin condition ( J:75413 )

thin skin ( J:75413 )