Phenotypes associated with this allele

• Allele Symbol: Tg(CAG-cat,-Ptpn11*Q97R)1Rbns
• Allele Name: transgene insertion 1, Jeffrey Robbins
• Allele ID: MGI:3822129
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mapk1^tm1Melo/Mapk1^+ Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N	MGI:3822161
cn2	Mapk3^tm1Gpg/Mapk3^tm1Gpg Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: 129/Sv * C3H * C57BL/6 * FVB/N	MGI:3822162
cn3	Mapk3^tm1Gpg/Mapk3^+ Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: 129/Sv * C3H * C57BL/6 * FVB/N	MGI:3822163
cn4	Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0 Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6 * FVB/N	MGI:3822157
cn5	H2az2^Tg(Wnt1-cre)11Rth/H2az2^+ Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0	involves: C57BL/6J * CBA/J * FVB/N	MGI:4361520

Genotype
MGI:3822161

cn1

• Allelic Composition: Mapk1^tm1Melo/Mapk1⁺; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:142212 )

• all mice died by E14.5

cardiovascular system

increased atrioventricular cushion size ( J:142212 )

double outlet right ventricle ( J:142212 )

• the frequency of double outlet right ventricles is greater than in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice

ventricular septal defect ( J:142212 )

• the frequency of ventricular septal defects is greater than in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice

abnormal cardiovascular system physiology ( J:142212 )

• proliferation of endothelial, mesenchymal, and cardiomyocyte cells is increased while apoptosis rates are decreased compared to in wild-type

liver/biliary system

hepatic necrosis ( J:142212 )

homeostasis/metabolism

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

integument

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

growth/size/body

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

Genotype
MGI:3822162

cn2

• Allelic Composition: Mapk3^tm1Gpg/Mapk3^tm1Gpg; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129/Sv * C3H * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:142212 )

• all mice died by E14.5

• however, Mendelian ratios of embryos are present at E13.5

cardiovascular system

cardiovascular system phenotype ( J:142212 )

N • mice exhibit normal endocardial cushion size and rates of proliferation and apoptosis of endothelial and mesenchymal cushion cells

liver/biliary system

hepatic necrosis ( J:142212 )

homeostasis/metabolism

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

integument

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

growth/size/body

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

Genotype
MGI:3822163

cn3

• Allelic Composition: Mapk3^tm1Gpg/Mapk3⁺; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: 129/Sv * C3H * C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:142212 )

• all mice died by E14.5

cardiovascular system

increased atrioventricular cushion size ( J:142212 )

• endocardial cushion volume is increased compared to in wild-type mice but not as severely as in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice

liver/biliary system

hepatic necrosis ( J:142212 )

homeostasis/metabolism

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

integument

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

growth/size/body

nuchal edema ( J:142212 )

• mice exhibit nuchal edema

Genotype
MGI:3822157

cn4

• Allelic Composition: Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6 * FVB/N

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:142212 )

• all mice died by E14.5

embryonic lethality during organogenesis, incomplete penetrance ( J:142212 )

• fewer than expected mice are present at E13.5 and no mice are present after birth

cardiovascular system

conotruncal ridge hyperplasia ( J:142212 )

• outflow tract cushion volume is only increased by 39% compared to in wild-type mice

abnormal atrioventricular cushion morphology ( J:142212 )

• at E13.5, valve primordial has not yet undergone differentiation and extracellular remodeling as in wild-type mice

increased atrioventricular cushion size ( J:142212 )

• cushion volume is increased up to 85% compared to in wild-type mice

double outlet right ventricle ( J:142212 )

• in some mice

ventricular septal defect ( J:142212 )

• in some mice

abnormal cardiovascular system physiology ( J:142212 )

• proliferation of endothelial, mesenchymal, and cardiomyocyte cells is increased compared to in wild-type

• proliferation of cells in the atrioventricular canal cushion endothelial and mesenchymal cell proliferation is increased while apoptosis is decreased compared to in wild-type mice

• however, proliferation of cardiomyocytes in the atrioventricular canal cushion is normal

hemorrhage ( J:142212 )

• at E13.5

ventricular cardiomyopathy ( J:142212 )

• some mice exhibit ventricular noncompaction

embryo

decreased embryo size ( J:142212 )

• at E13.5

growth/size/body

decreased embryo size ( J:142212 )

• at E13.5

nuchal edema ( J:142212 )

• at E13.5

homeostasis/metabolism

edema ( J:142212 )

• at E13.5, mice exhibit nuchal and back edema

nuchal edema ( J:142212 )

• at E13.5

liver/biliary system

small liver ( J:142212 )

• at E13.5

hepatic necrosis ( J:142212 )

muscle

ventricular cardiomyopathy ( J:142212 )

• some mice exhibit ventricular noncompaction

integument

nuchal edema ( J:142212 )

• at E13.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 1		DOID:0060578	OMIM:163950	J:142212

Genotype
MGI:4361520

cn5

• Allelic Composition: H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺; Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0
• Genetic Background: involves: C57BL/6J * CBA/J * FVB/N

mortality/aging

postnatal lethality ( J:153094 )

• mice that exhibit a cleft palate die within 5 days of birth

craniofacial

abnormal craniofacial morphology ( J:153094 )

• mice exhibit craniofacial defects that become more pronounced with age

• however, treatment with U0126 restores skull size, length, mandibular bone length, inner canthal distance, and frontal bone height

abnormal cranium morphology ( J:153094 )

• at E17.5 and P2, mice exhibit abnormal skull morphology

• however, treatment with U0126 restores skull size, length, mandibular bone length, inner canthal distance, and frontal bone height

large anterior fontanelle ( J:153094 )

• mice exhibit larger than normal anterior fontanelle

• however, treatment with U0126 restores normal anterior fontanelle morphology

decreased cranium height ( J:153094 )

• mice exhibit a reduced skull length compared to in wild-type mice

• however, treatment with U0126 restores frontal bone morphology

abnormal frontal bone morphology ( J:153094 )

• mice exhibit taller frontal bone heights compared with wild-type mice

• however, treatment with U0126 restores frontal bone morphology

short mandible ( J:153094 )

• proportional to the small skull length

• however, treatment with U0126 restores mandible length

domed cranium ( J:153094 )

• dome-shaped head

cleft upper lip ( J:153094 )

• in 21% of mice

cleft palate ( J:153094 )

• in 21% of mice

abnormal nose morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

abnormal nasal cartilage morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

broad snout ( J:153094 )

• mice have a broad nose

lowered ear position ( J:153094 )

skeleton

abnormal cranium morphology ( J:153094 )

• at E17.5 and P2, mice exhibit abnormal skull morphology

• however, treatment with U0126 restores skull size, length, mandibular bone length, inner canthal distance, and frontal bone height

large anterior fontanelle ( J:153094 )

• mice exhibit larger than normal anterior fontanelle

• however, treatment with U0126 restores normal anterior fontanelle morphology

decreased cranium height ( J:153094 )

• mice exhibit a reduced skull length compared to in wild-type mice

• however, treatment with U0126 restores frontal bone morphology

abnormal frontal bone morphology ( J:153094 )

• mice exhibit taller frontal bone heights compared with wild-type mice

• however, treatment with U0126 restores frontal bone morphology

short mandible ( J:153094 )

• proportional to the small skull length

• however, treatment with U0126 restores mandible length

domed cranium ( J:153094 )

• dome-shaped head

abnormal nasal cartilage morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

growth/size/body

cleft upper lip ( J:153094 )

• in 21% of mice

cleft palate ( J:153094 )

• in 21% of mice

abnormal nose morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

abnormal nasal cartilage morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

broad snout ( J:153094 )

• mice have a broad nose

lowered ear position ( J:153094 )

decreased body weight ( J:153094 )

• mice exhibit a reduced body weight that is partially restored by treatment with U0126

webbed neck ( J:153094 )

• webbed neck

decreased body height ( J:153094 )

• mice exhibit a short stature that is partially restored by treatment with U0126

postnatal growth retardation ( J:153094 )

• pronounced at P2

decreased fetal size ( J:153094 )

• slightly at E17.5

embryo

abnormal neural crest cell migration ( J:153094 )

• neural crest cells fail to contribute to the parietal bone unlike in wild-type mice

hearing/vestibular/ear

lowered ear position ( J:153094 )

vision/eye

ocular hypertelorism ( J:153094 )

• mice exhibit hypetelorism compared with wild-type mice

increased inner canthal distance ( J:153094 )

• mice exhibit a greater inner canthal distance compared with wild-type mice

• however, treatment with U0126 restores inner canthal distance

digestive/alimentary system

cleft palate ( J:153094 )

• in 21% of mice

respiratory system

abnormal nose morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

abnormal nasal cartilage morphology ( J:153094 )

• nasal cartilage and bones do not fuse along the midline unlike in wild-type mice

integument

webbed neck ( J:153094 )

• webbed neck

cellular

abnormal neural crest cell migration ( J:153094 )

• neural crest cells fail to contribute to the parietal bone unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome 1		DOID:0060578	OMIM:163950	J:153094