Phenotypes Associated with This Genotype

Genotype
MGI:6401000

• Allelic Composition: Dpp4^{tm1.1(DPP4)Pbmj}/Dpp4^{tm1.1(DPP4)Pbmj}
• Genetic Background: involves: C57BL/6 * C57BL/6NTac

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

immune system

lung inflammation ( J:242025 )

• mice infected with MERS-MA show mild inflammatory cell infiltrates in perivascular regions and alveolar septa at 1 and 3 days post infection (dpi), with mild and uncommon multifocal mononuclear cell infiltrates at 4 and 5 dpi

• mice infected with the parental MERS-CoV show mild inflammatory cell infiltrates in perivascular regions and alveolar septa at 1 and 3 dpi and multifocal mononuclear cell infiltrates at 4 and 5 dpi

• mice infected with MERS-MA show a greater accumulation of activated inflammatory monocyte-macrophages and neutrophils but fewer lymphocytes in the lungs than infection with MERS-CoV

• higher numbers of NK-, T-, and B-cells are seen in the lungs of MERS-CoV-infected mice compared to MERS-MA-infected mice

• both mice infected with MERS-MA and MERS-CoV exhibit an increase in reactive lymphocytes

increased susceptibility to Coronaviridae infection ( J:242025 )

• mice intranasally infected with 10⁴-10⁶ pfu Middle East respiratory syndrome coronavirus (MERS-CoV; EMC/2012, Vero 81 cell passaged) show virus replication in the lung but no weight loss or mortality

• lung virus titers of mice infected with the mouse-adapted MERS-CoV, MERS-MA (obtained after 30 in vivo passages of the virus in mutant mice) are about 1-2 log higher than those challenged with the MERS-CoV parental virus and virus is detected in the serum, however, no virus is detected in the brain or other organs although a low-level virus genomic RNA was detected in the liver

• mice infected with MERS-MA show weight loss, multifocal hyaline membranes, edema, and necrotic debris indicating diffuse alveolar damage

• mice infected with MERS-MA show delayed, but greater increases in type I and III interferons and more robust cytokine/chemokine responses that those infected with the parental MERS-CoV

• MERS-MA challenged mice show an overt and injurious innate inflammatory response and a suboptimal adaptive immune response

• lungs of mice infected with MERS-MA show lower absolute numbers of CD45+ leukocytes compared to MERS-CoV-infected mice or uninfected controls

• peripheral blood from MERS-MA-infected mice shows monocyte activation, reduced erythrocyte density, and reduced polychromatophils (immature RBCs) indicating anemia of inflammation

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:242025 )

• after 21 in vivo passages of the MERS-CoV virus in mutant mice, virus inoculum causes approximate 50% mortality

• after 30 in vivo passages of the virus (the mouse-adapted MERS-CoV, MERS-MA) in mutant mice, a 10⁴ pfu virus inoculum causes approximate 80% mortality

• mice inoculated with 10⁵ pfu of MERS-MA plaque-purified isolates show fatal disease; an inoculum of 5 x 10³ pfu is lethal

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:242025 )

• after 21 in vivo passages of the MERS-CoV virus in mutant mice, virus inoculum causes approximate 50% mortality

• after 30 in vivo passages of the virus (the mouse-adapted MERS-CoV, MERS-MA) in mutant mice, a 10⁴ pfu virus inoculum causes approximate 80% mortality

• mice inoculated with 10⁵ pfu of MERS-MA plaque-purified isolates show fatal disease; an inoculum of 5 x 10³ pfu is lethal

respiratory system

pulmonary edema ( J:242025 )

• mice infected with MERS-MA develop pulmonary edema

lung inflammation ( J:242025 )

• mice infected with MERS-MA show mild inflammatory cell infiltrates in perivascular regions and alveolar septa at 1 and 3 days post infection (dpi), with mild and uncommon multifocal mononuclear cell infiltrates at 4 and 5 dpi

• mice infected with the parental MERS-CoV show mild inflammatory cell infiltrates in perivascular regions and alveolar septa at 1 and 3 dpi and multifocal mononuclear cell infiltrates at 4 and 5 dpi

• mice infected with MERS-MA show a greater accumulation of activated inflammatory monocyte-macrophages and neutrophils but fewer lymphocytes in the lungs than infection with MERS-CoV

• higher numbers of NK-, T-, and B-cells are seen in the lungs of MERS-CoV-infected mice compared to MERS-MA-infected mice

• both mice infected with MERS-MA and MERS-CoV exhibit an increase in reactive lymphocytes

pulmonary hyaline membrane formation ( J:242025 )

• mice infected with MERS-MA show multifocal hyaline membranes

cardiovascular system

increased vascular permeability ( J:242025 )

• MERS-MA infected lungs show increased vascular permeability at 4 and 5 dpi

homeostasis/metabolism

pulmonary edema ( J:242025 )

• mice infected with MERS-MA develop pulmonary edema

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Middle East respiratory syndrome		DOID:0080642		J:242025