Phenotypes Associated with This Genotype

Genotype
MGI:6402203

• Allelic Composition: Tg(KRT18-DPP4)3Pbmj/0
• Genetic Background: involves: C57BL/6J * SJL/J

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

immune system

abnormal mononuclear cell morphology ( J:286231 )

♀ • intragastrically MERS-CoV incoculated mice show increased mononuclear cell infiltration in the lamina propria of the small intestine and alveolar septa

increased lymphocyte cell number ( J:286231 )

♀ • intragastrically MERS-CoV incoculated mice show an increase in CD3+ lymphocytes

abnormal cytokine secretion ( J:285467 )

• MERS-CoV infected mice show induction of proinflammatory cytokines

brain inflammation ( J:285467 )

• brains of MERS-CoV infected mice show perivascular cuffing after 2 dpi

lung inflammation ( J:286231 , J:285467 )

• lungs of MERS-CoV infected mice produce patchy consolidation variably composed of cellular inflammation, vascular congestion, and atelectasis (J:285467)

♀ • pantoprazole pretreated intragastrically MERS-CoV inoculated mice show prominent pulmonary inflammation 5 days post infection (dpi) while mice show inflammatory infiltration in the lung at 8 dpi without pantoprazole pretreatment (J:286231)

interstitial pneumonia ( J:286231 )

♀ • intragastrically MERS-CoV inoculated mice show marked infiltration of mononuclear cells and lymphocytes in the alveolar septa, indicating interstitial inflammation

increased susceptibility to Coronaviridae infection ( J:286231 , J:285467 )

• mice infected with MERS-CoV exhibit weight loss, hypothermia, and die at 6-7 days post infection (dpi) (J:285467)

• viral titers are highest in lung tissues at 2dpi and then decline while in the brain, viral titers are undetectable at 2 dpi but then increase at 4 and 6 dpi (J:285467)

• virus RNA is detected in the lung and brain and lower levels in the spleen, kidney and heart even though no virus was titered from the kidney (J:285467)

• MERS-CoV is not transmitted from infected transgenic mice to uninfected transgenic mice housed in the same cages (J:285467)

• mice vaccinated with Venezuelan equine encephalitis replicon particles expressing the MERS-CoV surface S glycoprotein (VPR-S) are completely protected against lethal infection (J:285467)

• mice pretreated with serum from mice immunized with VPR-S a day before MERS-CoV infection are completely protected against lethal infection and this passive immunization completely prevents spread of infection to the brain (J:285467)

♀ • mice inoculated intragastrically with MERS-CoV strain EMC/2012 show partial penetrance of weight loss and lethal infection and increased viral load in the intestine (J:286231)

♀ • mice treated with pantoprazole (to improve viability of MERS-CoV in the stomach) prior to MERS-CoV intragastrical inoculation show more extensive intestinal and lung pathology and greater viral load in the small intestine compared to non-pantoprazole treated mice (J:286231)

♀ • mice directly injected with MERS-CoV into the stomach (intragastic injection) after a minor laparotomy show elevated viral load in the small intestine, lungs, and brain (J:286231)

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:286231 , J:285467 )

• mice infected with the EMC2012 strain of the Middle East respiratory-coronavirus (MERS-CoV) die at 6-7 days post infection (J:285467)

• mortality of MERS-CoV-infected mice correlates with brain infection (J:285467)

♀ • mice inoculated intragastrically with MERS-CoV show partial penetrance of lethal infection (J:286231)

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:286231 , J:285467 )

• mice infected with the EMC2012 strain of the Middle East respiratory-coronavirus (MERS-CoV) die at 6-7 days post infection (J:285467)

• mortality of MERS-CoV-infected mice correlates with brain infection (J:285467)

♀ • mice inoculated intragastrically with MERS-CoV show partial penetrance of lethal infection (J:286231)

hematopoietic system

abnormal mononuclear cell morphology ( J:286231 )

♀ • intragastrically MERS-CoV incoculated mice show increased mononuclear cell infiltration in the lamina propria of the small intestine and alveolar septa

increased lymphocyte cell number ( J:286231 )

♀ • intragastrically MERS-CoV incoculated mice show an increase in CD3+ lymphocytes

respiratory system

abnormal lung vasculature morphology ( J:285467 )

• some lungs of MERS-CoV infected mice show thrombi, with nearby vascular congestion and lesser hemorrhage and necrosis

pulmonary vascular congestion ( J:285467 )

• lungs of MERS-CoV infected mice produce patchy consolidation variably composed of cellular inflammation, vascular congestion, and atelectasis

pulmonary alveolar edema ( J:285467 )

• lungs of some MERS-CoV infected mice show alveolar edema

lung inflammation ( J:286231 , J:285467 )

• lungs of MERS-CoV infected mice produce patchy consolidation variably composed of cellular inflammation, vascular congestion, and atelectasis (J:285467)

♀ • pantoprazole pretreated intragastrically MERS-CoV inoculated mice show prominent pulmonary inflammation 5 days post infection (dpi) while mice show inflammatory infiltration in the lung at 8 dpi without pantoprazole pretreatment (J:286231)

interstitial pneumonia ( J:286231 )

♀ • intragastrically MERS-CoV inoculated mice show marked infiltration of mononuclear cells and lymphocytes in the alveolar septa, indicating interstitial inflammation

atelectasis ( J:285467 )

• lungs of MERS-CoV infected mice produce patchy consolidation variably composed of cellular inflammation, vascular congestion, and atelectasis

cardiovascular system

abnormal lung vasculature morphology ( J:285467 )

• some lungs of MERS-CoV infected mice show thrombi, with nearby vascular congestion and lesser hemorrhage and necrosis

pulmonary vascular congestion ( J:285467 )

• lungs of MERS-CoV infected mice produce patchy consolidation variably composed of cellular inflammation, vascular congestion, and atelectasis

homeostasis/metabolism

pulmonary alveolar edema ( J:285467 )

• lungs of some MERS-CoV infected mice show alveolar edema

nervous system

brain inflammation ( J:285467 )

• brains of MERS-CoV infected mice show perivascular cuffing after 2 dpi

neuronal cytoplasmic inclusions ( J:285467 )

• degenerating neurons of MERS-CoV infected mice sometimes have basophilic cytoplasmic inclusions

neurodegeneration ( J:285467 )

• brains of MERS-CoV infected mice show cellular degeneration and debris after 2 dpi

• MERS-CoV-induced neuronal lesions are most severe in the thalamus and brain stem

renal/urinary system

abnormal kidney morphology ( J:285467 )

• MERS-CoV-infected mice show scattered-to-patchy tubular injury, including tubular dilation, cell sloughing/debris, and cellular necrosis late in the course of infection

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:286231 )

♀ • intragastrically MERS-CoV incoculated mice show increased sloughing of the surface epithelium

abnormal small intestine morphology ( J:286231 )

♀ • the small intestine of intragastrically MERS-CoV incoculated mice shows deteriorating inflammation and epithelial degeneration

♀ • mice treated with pantoprazole (to improve viability of MERS-CoV in the stomach) prior to MERS-CoV intragastrical inoculation show more extensive and prominent pathology in the small intestine

abnormal small intestinal villus morphology ( J:286231 )

♀ • intragastrically MERS-CoV incoculated mice show broadening of the intestinal villi

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Middle East respiratory syndrome		DOID:0080642		J:286231 , J:285467