Phenotypes Associated with This Genotype

Genotype
MGI:3690223

• Allelic Composition: Serpine1^tm1Mlg/Serpine1^tm1Mlg
• Genetic Background: B6.129S2-Serpine1^tm1Mlg/J

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

cardiovascular system

increased angiogenesis ( J:108675 )

• aortic vessel explants show increased capillary sprouting in both collagen lattices and Matrigel

cardiac fibrosis ( J:101486 )

• older mutants develop cardiac fibrosis, however fibrosis is not seen in the liver, spleen, lungs or kidneys and do not develop small vessel disease

lung hemorrhage ( J:288556 )

• SARS-CoV MA15-infected mice show increased lung hemorrhage at 7 dpi

heart inflammation ( J:101486 )

• older mutants exhibit significantly more macrophages in the heart

respiratory system

lung hemorrhage ( J:288556 )

• SARS-CoV MA15-infected mice show increased lung hemorrhage at 7 dpi

immune system

heart inflammation ( J:101486 )

• older mutants exhibit significantly more macrophages in the heart

increased susceptibility to bacterial infection ( J:124327 )

• following infection with live Streptococcus pneumoniae, S. pneumoniae wild-type lysate, and S. pneumoniae pneumolysin (PLY), mice begin to die earlier and are all dead by 5 days post-infection

• following infection with S. pneumoniae, acute lung injury and alveolar hemorrhage is enhanced

• following infection with S. pneumoniae strain ATCC 6303 (a more virulent strain), mortality is increased (10% survival compared to 45% in wild-type mice)

increased susceptibility to Coronaviridae infection ( J:288556 )

• mice infected with a sublethal dose of mouse-adapted SARS-CoV MA15 continue to lose weight through day 7 postinfection, showing more weight loss than wild-type controls at 5-7 days post infection (dpi), decreased locomotion, hunched posture, and labored breathing

• SARS-CoV MA15-infected mice exhibit cuffing of inflammatory cells around the large airways and vasculature and mild interstitial membrane thickening and a few inflammatory cells in the alveolar spaces at 4 dpi, with moderate level of disease in the parenchyma by 7 dpi

• however, virus load of SARS-CoV MA15-infected mice is similar to wild-type controls

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:288556 )

• mice infected with a lethal dose of SARS-CoV MA15 succumb to infection sooner than wild-type controls

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:123733 )

• 3 weeks after BDL, urokinase plasminogen activator (uPA) and plasmin activity are not increased in mutants but tissue-type plasminogen activator (tPA) activity is significantly increased relative to wild-type

• 3 weeks after BDL, pro-MMP-9 and MMP-9 activities in liver homogenates from mutants are increased significantly compared to wild-type controls

liver/biliary system

liver/biliary system phenotype ( J:123733 )

N • stellate cell activation, TGFbeta-1 and collagen synthesis are similar in mutants and controls before and after bile duct ligation

liver fibrosis ( J:123733 )

• 3 weeks after bile duct ligation (BDL), hepatic fibrosis is reduced 18-26% compared to wild-type; hepatic collagen content is similar to sham-operated wild-type

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:288556 )

• mice infected with a lethal dose of SARS-CoV MA15 succumb to infection sooner than wild-type controls

increased susceptibility to induced morbidity/mortality ( J:124327 )

• following infection with live Streptococcus pneumoniae, S. pneumoniae wild-type lysate, and S. pneumoniae pneumolysin (PLY), mice begin to die earlier and are all dead by 5 days post-infection

• following infection with S. pneumoniae strain ATCC 6303 (a more virulent strain), mortality is increased (10% survival compared to 45% in wild-type mice)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Coronavirus infectious disease		DOID:0080599		J:288556