Phenotypes Associated with This Genotype

Genotype
MGI:6272304

• Allelic Composition: Myd88^tm1.1Defr/Myd88^tm1.1Defr
• Genetic Background: B6.129P2(SJL)-Myd88^tm1.1Defr

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

immune system

decreased leukocyte cell number ( J:224849 )

• infiltrating CD45hi leukocytes are reduced by about 50% in JHMV-infected mice at 3 and 5 dpi, with differences less prominent after 7 dpi

decreased neutrophil cell number ( J:224849 )

• infiltrating neutrophils (CD45hi Ly6G+) are reduced more than 60% in JHMV-infected mice at 3 and 5 dpi

decreased effector memory CD4-positive, alpha-beta T cell number ( J:224849 )

• CD4 T cell recruitment in the CNS is impaired in JHMV-infected mice, reaching only 50% or less of wild-type levels

• however, overall numbers of CD8 T cells in the CNS is not altered

decreased macrophage cell number ( J:224849 )

• infiltrating monocytes/macrophages (CD45hi F480+) are reduced by more than 70% in JHMV-infected mice at 3 and 5 dpi but increase subsequently

decreased monocyte cell number ( J:224849 )

• infiltrating monocytes/macrophages (CD45hi F480+) are reduced by more than 70% in JHMV-infected mice at 3 and 5 dpi but increase subsequently

abnormal CD4-positive, alpha-beta T cell physiology ( J:224849 )

• only about 7% of CNS-derived CD4 T cell population produces IFN-gamma compared to about 25% of wild-type CD4 T cells in JHMV-infected mice

• the percentage of IFN-gamma-producing CD4 T cells are reduced by about 50% in cervical lymph nodes of JHMV-infected mice

abnormal macrophage physiology ( J:224849 )

• infiltrating macrophages exhibit impaired and delayed MHC class II expression in JHMV-infected mice

abnormal microglial cell physiology ( J:224849 )

• microglia exhibit reduced MHC class II expression in JHMV-infected mice

decreased interferon-gamma secretion ( J:224849 )

• JHMV-infected mice show reduced IFN-gamma levels and activity in the CNS throughout infection

• only about 7% of CNS-derived CD4 T cell population produces IFN-gamma compared to about 25% of wild-type CD4 T cells in JHMV-infected mice

• the percentage of IFN-gamma-producing CD4 T cells are reduced by about 50% in cervical lymph nodes of JHMV-infected mice

increased susceptibility to Coronaviridae infection ( J:224849 )

• mice infected intracranially with a sublethal, gliatrophic, monoclonal antibody-derived variant of mouse hepatitis virus strain JHM (JHMV) 2.2v-1 develop more severe paralytic disease than wild-type mice and do not show signs of recovery by 14 days post infection (dpi)

• JHMV-infected mice show higher viral loads within the central nervous system at 5 dpi and show no viral control until 10 dpi, showing a modest reduction at 14 dpi

• the numbers of viral antigen+ cells in JHMV-infected mice are increased and foci are more widely distributed throughout the brain, the numbers of infected cells in white matter are increased, and viral dissemination to gray matter is seen

• however, JHMV-infected mice do not exhibit hepatitis

• JHMV-infected mice show diminished recruitment of inflammatory cells during early infection, showing less pronounced perivascular inflammation in the CNS, allowing for viral dissemination

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:224849 )

• mice infected with JHMV gradually succumb to infection with a survival rate of only about 10% by 21 dpi compared to 90% survival in wild-type mice

mortality/aging

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:224849 )

• mice infected with JHMV gradually succumb to infection with a survival rate of only about 10% by 21 dpi compared to 90% survival in wild-type mice

nervous system

abnormal microglial cell physiology ( J:224849 )

• microglia exhibit reduced MHC class II expression in JHMV-infected mice

demyelination ( J:224849 )

• JHMV-infected mice exhibit increased demyelination in the brain stem and spinal cord

behavior/neurological

paralysis ( J:224849 )

• JHMV-infected mice exhibit more severe paralysis than wild-type mice

hematopoietic system

decreased leukocyte cell number ( J:224849 )

• infiltrating CD45hi leukocytes are reduced by about 50% in JHMV-infected mice at 3 and 5 dpi, with differences less prominent after 7 dpi

decreased neutrophil cell number ( J:224849 )

• infiltrating neutrophils (CD45hi Ly6G+) are reduced more than 60% in JHMV-infected mice at 3 and 5 dpi

decreased effector memory CD4-positive, alpha-beta T cell number ( J:224849 )

• CD4 T cell recruitment in the CNS is impaired in JHMV-infected mice, reaching only 50% or less of wild-type levels

• however, overall numbers of CD8 T cells in the CNS is not altered

decreased macrophage cell number ( J:224849 )

• infiltrating monocytes/macrophages (CD45hi F480+) are reduced by more than 70% in JHMV-infected mice at 3 and 5 dpi but increase subsequently

decreased monocyte cell number ( J:224849 )

• infiltrating monocytes/macrophages (CD45hi F480+) are reduced by more than 70% in JHMV-infected mice at 3 and 5 dpi but increase subsequently

abnormal CD4-positive, alpha-beta T cell physiology ( J:224849 )

• only about 7% of CNS-derived CD4 T cell population produces IFN-gamma compared to about 25% of wild-type CD4 T cells in JHMV-infected mice

• the percentage of IFN-gamma-producing CD4 T cells are reduced by about 50% in cervical lymph nodes of JHMV-infected mice

abnormal macrophage physiology ( J:224849 )

• infiltrating macrophages exhibit impaired and delayed MHC class II expression in JHMV-infected mice

abnormal microglial cell physiology ( J:224849 )

• microglia exhibit reduced MHC class II expression in JHMV-infected mice