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Phenotypes Associated with This Genotype
Genotype
MGI:3771372
Allelic
Composition
Stat1tm1Rds/Stat1tm1Rds
Genetic
Background
129S6/SvEv-Stat1tm1Rds/Tac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Stat1tm1Rds mutation (4 available); any Stat1 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 30% of mice infected with the Urbani strain of severe acute respiratory syndrome coronavirus (SARS-CoV) do not recover by day 29 post-infection and die
• mice infected with a recombinant isogenic mouse-adapted SARS-CoV (rMA15) that contains six virulence modifying mutations succumb to lethal infection by day 9 which is not seen in wild-type controls

endocrine/exocrine glands
• 65% of nulliparous mice develop spontaneous mammary adenocarcinomas with a median tumor onset of 23 months
• 91% of multiparous mice develop mammary tumors with a median tumor onset of 14.8 months of age
• mammary tumors are estrogen receptor-alpha and progesterone receptor positive and HER2 negative and display display a surface marker phenotype reflective of luminal mammary tumors
• early lesions vary from distended ducts to small cystically dilated clusters of alveoli and contain atypical cells indicative of mammary intraepithelial neoplasia
• some tumors have invasive nests of neoplastic cells with areas of fibrosis and inflammation

digestive/alimentary system
• a fibrinous peritonitis develops in Urbani SARS-CoV-infected mice at 15-24 dpi

homeostasis/metabolism
• following exposure to ischemia/reperfusion
• unlike wild-type cells, primary neurons are resistant to interferon-gamma-induced neurotoxicity
• treatment with LPS and DGalN fail to induce an increase in serum interferon-gamma levels as in wild-type mice
• Urbani SARS-CoV-infected mice show edema around peribronchiolar blood vessels at 3 dpi
• the perivascular edema fluid has a blue tinge at 5 dpi, suggesting early collage deposition
• unlike in wild-type mice, treatment with LPS and DGalN or TNF-alpha and interferon-gamma fails to increase nitric oxide levels

respiratory system
• Urbani SARS-CoV-infected mice show more necrosis in the lungs than wild-type controls
• Urbani SARS-CoV-infected mice show edema around peribronchiolar blood vessels at 3 dpi
• the perivascular edema fluid has a blue tinge at 5 dpi, suggesting early collage deposition
• Urbani SARS-CoV-infected mice show more inflammation in the lungs than controls, with inflammatory cell infiltrate containing many lymphocytes and neutrophils with a few eosinophils and macrophages at 3 dpi, foci of regeneration in bronchiolar epithelium and less severe peribronchiolar and perivascular inflammation on 5 dpi, an increase in inflammatory cells around residual inflammatory lesions with abundant neutrophils and more macrophages in the lesions, epithelial hyperplasia in foci, bronchiolitis obliterans in some airways and the development of fibrinous pleuritis with pyogranulomatous lesions in 2 of 3 mice at 9 dpi
• rMA15-infected mice exhibit a more severe extent of lung inflammation, with a greater number of macrophages infiltrating into all areas of the lungs and thickening of the alveolar septa throughout the lungs with perivascular and peribronchial thickening
• rMA15-infected lungs show large foci containing densely packed fibroblasts, macrophages, and lymphocytes throughout the lungs and scattered atypical large cells throughout the foci
• Urbani SARS-CoV-infected mice develop bronchiolitis obliterans in some airways at 9 dpi
• Urbani SARS-CoV-infected mice develop a fibrinous pleuritis with pyogranulomatous lesions at 9 dpi
• rMA15-infected mice show pleuritis with a breakdown of the pleura

integument
• 65% of nulliparous mice develop spontaneous mammary adenocarcinomas with a median tumor onset of 23 months
• 91% of multiparous mice develop mammary tumors with a median tumor onset of 14.8 months of age
• mammary tumors are estrogen receptor-alpha and progesterone receptor positive and HER2 negative and display display a surface marker phenotype reflective of luminal mammary tumors
• early lesions vary from distended ducts to small cystically dilated clusters of alveoli and contain atypical cells indicative of mammary intraepithelial neoplasia
• some tumors have invasive nests of neoplastic cells with areas of fibrosis and inflammation

cardiovascular system
• following exposure to ischemia/reperfusion
• following exposure to ischemia/reperfusion

nervous system
• unlike wild-type cells, primary neurons are resistant to interferon-gamma-induced neurotoxicity

neoplasm
• 65% of nulliparous mice develop spontaneous mammary adenocarcinomas with a median tumor onset of 23 months
• 91% of multiparous mice develop mammary tumors with a median tumor onset of 14.8 months of age
• mammary tumors are estrogen receptor-alpha and progesterone receptor positive and HER2 negative and display display a surface marker phenotype reflective of luminal mammary tumors
• early lesions vary from distended ducts to small cystically dilated clusters of alveoli and contain atypical cells indicative of mammary intraepithelial neoplasia
• some tumors have invasive nests of neoplastic cells with areas of fibrosis and inflammation

muscle
• following exposure to ischemia/reperfusion

cellular
• following exposure to ischemia/reperfusion
• unlike wild-type cells, primary neurons are resistant to interferon-gamma-induced neurotoxicity
• unlike in wild-type mice, treatment with LPS and DGalN or TNF-alpha and interferon-gamma fails to increase hepatocyte apoptosis
• Urbani SARS-CoV-infected mice show more necrosis in the lungs than wild-type controls
• inhibition of RANKL induced osteoclastogenesis by flagellin and lipopolysaccharide is reversed
• unlike in wild-type mice, treatment with LPS and DGalN or TNF-alpha and interferon-gamma fails to increase the production of reactive oxygen species in hepatocytes

immune system
• inhibition of RANKL induced osteoclastogenesis by flagellin and lipopolysaccharide is reversed
• a fibrinous peritonitis develops in Urbani SARS-CoV-infected mice at 15-24 dpi
• unlike in wild-type mice, treatment with LPS and DGalN fails to decrease K T cell numbers
• macrophages exhibit impaired ability to kill Bacillus anthracis compared with wild-type cells
• treatment with LPS and DGalN fail to induce an increase in serum interferon-gamma levels as in wild-type mice
• following exposure of macrophages to LPS or Bacillus anthracis spores
• Urbani SARS-CoV-infected mice show more inflammation in the lungs than controls, with inflammatory cell infiltrate containing many lymphocytes and neutrophils with a few eosinophils and macrophages at 3 dpi, foci of regeneration in bronchiolar epithelium and less severe peribronchiolar and perivascular inflammation on 5 dpi, an increase in inflammatory cells around residual inflammatory lesions with abundant neutrophils and more macrophages in the lesions, epithelial hyperplasia in foci, bronchiolitis obliterans in some airways and the development of fibrinous pleuritis with pyogranulomatous lesions in 2 of 3 mice at 9 dpi
• rMA15-infected mice exhibit a more severe extent of lung inflammation, with a greater number of macrophages infiltrating into all areas of the lungs and thickening of the alveolar septa throughout the lungs with perivascular and peribronchial thickening
• rMA15-infected lungs show large foci containing densely packed fibroblasts, macrophages, and lymphocytes throughout the lungs and scattered atypical large cells throughout the foci
• Urbani SARS-CoV-infected mice develop bronchiolitis obliterans in some airways at 9 dpi
• Urbani SARS-CoV-infected mice develop a fibrinous pleuritis with pyogranulomatous lesions at 9 dpi
• rMA15-infected mice show pleuritis with a breakdown of the pleura
• mice exhibit increased susceptibility to infection with the Urbani strain of severe acute respiratory syndrome coronavirus (SARS-CoV) , with mice initially gaining more weight than wild-type mice through day 12 post-infection but then losing weight and showing worsening clinical disease over the next 15 days and 30% do not recover by day 29 post-infection and die
• virus in Urbani SARS-CoV-infected mice spreads from the respiratory tract into the spleen and liver
• Urbani SARS-CoV-infected mice show increased virus titers in the lungs at 15 dpi compared to wild-type mice in which virus is detectable only through 5 dpi
• mice exhibit increased susceptibility to infection with a recombinant isogenic mouse-adapted SARS-CoV (rMA15) that contains six virulence modifying mutations, losing 15% of their weight by day 4 and continue to lose weight through day 9 post infection and become moribund as weight loss approaches 30% and exhibit pathology resembling proliferate and organizing phase diffuse alveolar damage
• rMA15-infected mice show higher peak virus titers in the lungs at day 2 that remain high at 9 days post-infection (dpi) compared to wild-type mice which clear the virus by 9 dpi
• 30% of mice infected with the Urbani strain of severe acute respiratory syndrome coronavirus (SARS-CoV) do not recover by day 29 post-infection and die
• mice infected with a recombinant isogenic mouse-adapted SARS-CoV (rMA15) that contains six virulence modifying mutations succumb to lethal infection by day 9 which is not seen in wild-type controls

hematopoietic system
• inhibition of RANKL induced osteoclastogenesis by flagellin and lipopolysaccharide is reversed
• unlike in wild-type mice, treatment with LPS and DGalN fails to decrease K T cell numbers
• macrophages exhibit impaired ability to kill Bacillus anthracis compared with wild-type cells

skeleton
• inhibition of RANKL induced osteoclastogenesis by flagellin and lipopolysaccharide is reversed

liver/biliary system
• unlike in wild-type mice, treatment with LPS and DGalN or TNF-alpha and interferon-gamma fails to increase hepatocyte apoptosis

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
breast cancer DOID:1612 OMIM:114480
J:216040
severe acute respiratory syndrome DOID:2945 J:286237


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
09/07/2021
MGI 6.17
The Jackson Laboratory