Mouse Genome Informatics
cn1
    Mapk3tm1Gpg/Mapk3tm1Gpg
Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0
Tg(Tek-cre)12Flv/0

involves: 129/Sv * C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice died by E14.5
• however, Mendelian ratios of embryos are present at E13.5

cardiovascular system
N
• mice exhibit normal endocardial cushion size and rates of proliferation and apoptosis of endothelial and mesenchymal cushion cells (J:142212)

liver/biliary system

homeostasis/metabolism
• mice exhibit nuchal edema

integument
• mice exhibit nuchal edema

growth/size
• mice exhibit nuchal edema


Mouse Genome Informatics
cn2
    Mapk3tm1Gpg/Mapk3+
Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0
Tg(Tek-cre)12Flv/0

involves: 129/Sv * C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• 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

homeostasis/metabolism
• mice exhibit nuchal edema

integument
• mice exhibit nuchal edema

growth/size
• mice exhibit nuchal edema


Mouse Genome Informatics
cn3
    Mapk1tm1Melo/Mapk1+
Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0
Tg(Tek-cre)12Flv/0

involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• the frequency of double outlet right ventricles is greater than in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice
• the frequency of ventricular septal defects is greater than in Tg(CAG-cat,-Ptpn11*Q97R)1Rbns Tg(Tek-cre)12Flv mice
• proliferation of endothelial, mesenchymal, and cardiomyocyte cells is increased while apoptosis rates are decreased compared to in wild-type

liver/biliary system

homeostasis/metabolism
• mice exhibit nuchal edema

integument
• mice exhibit nuchal edema

growth/size
• mice exhibit nuchal edema


Mouse Genome Informatics
cn4
    Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0
Tg(Tek-cre)12Flv/0

involves: C3H * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected mice are present at E13.5 and no mice are present after birth

cardiovascular system
• at E13.5, valve primordial has not yet undergone differentiation and extracellular remodeling as in wild-type mice
• cushion volume is increased up to 85% compared to in wild-type mice
• outflow tract cushion volume is only increased by 39% compared to in wild-type mice
• in some mice
• 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
• at E13.5
• some mice exhibit ventricular noncompaction

embryogenesis

growth/size
• at E13.5

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

liver/biliary system
• at E13.5

muscle
• some mice exhibit ventricular noncompaction

integument
• at E13.5

Mouse Models of Human Disease
OMIM IDRef(s)
Noonan Syndrome 1; NS1 163950 J:142212


Mouse Genome Informatics
cn5
    Tg(CAG-cat,-Ptpn11*Q97R)1Rbns/0
Tg(Wnt1-cre)11Rth/0

involves: C57BL/6J * CBA/J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice that exhibit a cleft palate die within 5 days of birth

craniofacial
• 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
• 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
• mice exhibit a reduced skull length compared to in wild-type mice
• however, treatment with U0126 restores frontal bone morphology
• mice exhibit larger than normal anterior fontanelle
• however, treatment with U0126 restores normal anterior fontanelle morphology
• mice exhibit taller frontal bone heights compared with wild-type mice
• however, treatment with U0126 restores frontal bone morphology
• proportional to the small skull length
• however, treatment with U0126 restores mandible length
• dome-shaped head
• nasal bones fails to fuse along the midline unlike in wild-type mice
• mice have a broad nose
• nasal cartilage fails to fuse along the midline unlike in wild-type mice
• in 21% of mice
• in 21% of mice

skeleton
• 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
• mice exhibit a reduced skull length compared to in wild-type mice
• however, treatment with U0126 restores frontal bone morphology
• mice exhibit larger than normal anterior fontanelle
• however, treatment with U0126 restores normal anterior fontanelle morphology
• mice exhibit taller frontal bone heights compared with wild-type mice
• however, treatment with U0126 restores frontal bone morphology
• proportional to the small skull length
• however, treatment with U0126 restores mandible length
• dome-shaped head
• nasal cartilage fails to fuse along the midline unlike in wild-type mice

growth/size
• mice exhibit a reduced body weight that is partially restored by treatment with U0126
• webbed neck
• mice exhibit a short stature that is partially restored by treatment with U0126
• pronounced at P2
• slightly at E17.5

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

hearing/vestibular/ear

vision/eye
• mice exhibit hypetelorism and a greater inner canthal distance compared with wild-type mice
• however, treatment with U0126 restores inner canthal distance

digestive/alimentary system
• in 21% of mice

respiratory system
• nasal bones fails to fuse along the midline unlike in wild-type mice
• mice have a broad nose
• nasal cartilage fails to fuse along the midline unlike in wild-type mice

integument
• webbed neck

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

Mouse Models of Human Disease
OMIM IDRef(s)
Noonan Syndrome 1; NS1 163950 J:153094