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Phenotypes Associated with This Genotype
Genotype
MGI:6400425
Allelic
Composition
Dpp4em1Rba/Dpp4em1Rba
Genetic
Background
C57BL/6J-Dpp4em1Rba
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dpp4em1Rba mutation (0 available); any Dpp4 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• MERS-CoV maM35C4-infected mice show elevated numbers and frequencies of neutrophils by 2 dpi and remain elevated but slowly wane
• MERS-CoV maM35C4-infected mice show reduced numbers of lymphocytes on 2-4 dpi
• MERS-CoV maM35C4-infected mice show elevated numbers and frequencies of monocytes by 2 dpi
• inflammatory infiltrates are seen in the lungs of mice infected with MERS-15 intranasally at day 3 post infection
• mice infected with a mouse adapted MERS-CoV strain maM35C4 lose weight over time, and show rapid and high viral titers in lung tissue peaking 2 days post-infection (dpi) and reducing slightly by 4 dpi (J:279723)
• neutrophil numbers on 1 dpi in peripheral blood of mice infected with a lethal dose of MERS-CoV is predictive of disease severity (J:279723)
• mice support efficient infection and replication of the human Middle East respiratory syndrome coronavirus (MERS-CoV) strain HCoV-EMC/2012 , camel strain Dromedary/Al-Hasa-KFU-HKU13/2013 , and recombinant virus derived from a molecular infectious clone (icMERS) in the lungs which is not seen in wild-type controls (J:279834)
• a MERS-CoV tissue-culture adapted variant with a 3 amino acid insertion (RMR) and single amino acid change in the S2 region (S885L), MERS-0, shows enhanced replication in the lungs of mice, with mice showing nucleocapsid antigen from MERS-0 in the lungs and lungs showing moderate respiratory pathology and inflammation but no severe clinical disease symptoms (J:279834)
• mice infected with MERS-15, a mouse adapted MERS-CoV (MERS-0) via serial passage for 15 rounds through the lungs of heterozygous Dpp4em1Rba mice, intranasally show higher levels of MERS-15 replication in the lungs at 3 and 6 days post infection, while MERS-0 is cleared from the lungs by 6 days post infection and no replication is seen in wild-type mice (J:279834)
• however, no viral transcripts are seen in the brains of MERS-15 infected mice (J:279834)
• infection with one of two viral clones, MERS-15 C1 (containing mutations in nsP2 and a deletion from orf4b into orf5) or MERS-15 C2 (containing mutations in nsP2, nsP6, and nsP8, and a large deletion in orf4b), results in increased mortality, increased hemorrhage, 25-30% weight loss, high levels of virus replication, and lung pathology, with higher mortality and hemorrhage seen with MERS-15 C2 infection than MERS-15 C1 infection (J:279834)
• treatment of mice with human 3B11 antibody targeting the receptor-binding domain of the MERS-CoV spike protein provides 100% protection against MERS-15 C2 challenge (J:279834)
• mice vaccinated with Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein show protection from developing severe respiratory disease and lethal MERS-15 C2 infection challenge (J:279834)
• intranasal infection of mice with the MERS-15, a mouse adapted MERS-CoV (MERS-0) via serial passage for 15 rounds through the lungs of heterozygous Dpp4em1Rba mice, results in approximate 70% mortality
• infection with one of two viral clones, MERS-15 C1 (containing mutations in nsP2 and a deletion from orf4b into orf5) or MERS-15 C2 (containing mutations in nsP2, nsP6, and nsP8, and a large deletion in orf4b), results in increased mortality, with higher mortality with MERS-15 C2 infection than MERS-15 C1 infection

mortality/aging
• intranasal infection of mice with the MERS-15, a mouse adapted MERS-CoV (MERS-0) via serial passage for 15 rounds through the lungs of heterozygous Dpp4em1Rba mice, results in approximate 70% mortality
• infection with one of two viral clones, MERS-15 C1 (containing mutations in nsP2 and a deletion from orf4b into orf5) or MERS-15 C2 (containing mutations in nsP2, nsP6, and nsP8, and a large deletion in orf4b), results in increased mortality, with higher mortality with MERS-15 C2 infection than MERS-15 C1 infection

respiratory system
• severe hemorrhage in the lungs is seen in mice infected with MERS-15 intranasally at days 3 and 6 post infection
• mice infected with MERS-15 intranasally show intra-alveolar edema
• inflammatory infiltrates are seen in the lungs of mice infected with MERS-15 intranasally at day 3 post infection
• mice infected with MERS-15 intranasally show hyaline membrane formation at day 6 post infection
• mice infected with MERS-15 intranasally show increased enhanced pause (Penh), a measure reflecting airway obstruction/restriction due to debris in the airway, and increased midtidal expiratory flow (EF50), representing the flow rate at which 50% of tidal volume is expelled in a single breath, up to day 6 post infection indicating severe respiratory distress
• mice infected with MERS-15 intranasally show pathology associated with severe acute respiratory distress, including hyaline membrane formation, intra-alveolar edema, perivascular cuffing and severe inflammation at day 6 post infection

cardiovascular system
• severe hemorrhage in the lungs is seen in mice infected with MERS-15 intranasally at days 3 and 6 post infection

growth/size/body
• mice infected with MERS-15 intranasally show 20-25% weight loss by days 6 post infection compared to mice infected with MERS-0 or wild-type mice injected with MERS-15

homeostasis/metabolism
N
• blood glucose levels are normal
• mice infected with MERS-15 intranasally show intra-alveolar edema

hematopoietic system
• MERS-CoV maM35C4-infected mice show elevated numbers and frequencies of neutrophils by 2 dpi and remain elevated but slowly wane
• MERS-CoV maM35C4-infected mice show reduced numbers of lymphocytes on 2-4 dpi
• MERS-CoV maM35C4-infected mice show elevated numbers and frequencies of monocytes by 2 dpi

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Middle East respiratory syndrome DOID:0080642 J:279723 , J:279834


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