Analysis Tools
immune system
| N |
• homozygotes are viable and display normal myeloid and lymphoid immune cell compartments in the bone marrow, spleen, and lymph nodes
• frequencies and numbers of B and T cells, neutrophils, monocytes, or macrophages are normal
• no obvious signs of pathology are observed under homeostatic conditions
|
|
• purified neutrophils from homozygous mutant mice show a specific increase in MSU-triggered ROS production, but not in zymosan-induced ROS generation, relative to similarly-treated heterozygous controls
• homozygous mutant neutrophils show enhanced phosphorylation of the NADPH oxidase subunit p40phox after MSU treatment, but not after zymosan stimulation
• after injection of MSU crystals into the peritoneum, homozygotes show a significantly increased neutrophil influx relative to similarly-treated wild-type controls; in contrast, LPS-induced neutrophil recruitment is not significantly altered
• after injection of freeze-thawed dead kidney cells into the peritoneum, homozygotes show a significantly increased neutrophil influx relative to similarly-treated wild-type controls
• after X-ray irradiation with 1 Gy to induce double-positive thymocyte killing, homozygotes show enhanced infiltration of neutrophils into the thymus relative to similarly-treated wild-type controls
|
|
• X-ray irradiated homozygotes display increased expression of chemokines CXCL1 and CXCL10 relative to similarly-treated wild-type controls
|
|
• X-ray irradiated homozygotes display increased TNF expression relative to similarly-treated wild-type controls
|
|
• homozygotes display hyperinflammatory responses following challenge with MSU or necrotic cells and after radiation-induced thymocyte killing
|
cellular
|
• after challenge with uric acid crystals (monosodium urate, MSU) in the presence of luminol, homozygous mutant bone marrow cells show significantly increased ROS generation relative to similarly-treated heterozygous controls
• purified neutrophils from homozygous mutant mice show a specific increase in MSU-triggered ROS production, but not in zymosan-induced ROS generation, relative to similarly-treated heterozygous controls
|
hematopoietic system
|
• purified neutrophils from homozygous mutant mice show a specific increase in MSU-triggered ROS production, but not in zymosan-induced ROS generation, relative to similarly-treated heterozygous controls
• homozygous mutant neutrophils show enhanced phosphorylation of the NADPH oxidase subunit p40phox after MSU treatment, but not after zymosan stimulation
• after injection of MSU crystals into the peritoneum, homozygotes show a significantly increased neutrophil influx relative to similarly-treated wild-type controls; in contrast, LPS-induced neutrophil recruitment is not significantly altered
• after injection of freeze-thawed dead kidney cells into the peritoneum, homozygotes show a significantly increased neutrophil influx relative to similarly-treated wild-type controls
• after X-ray irradiation with 1 Gy to induce double-positive thymocyte killing, homozygotes show enhanced infiltration of neutrophils into the thymus relative to similarly-treated wild-type controls
|
|
• after challenge with uric acid crystals (monosodium urate, MSU) in the presence of luminol, homozygous mutant bone marrow cells show significantly increased ROS generation relative to similarly-treated heterozygous controls, consistent with the engagement of Clec12a by MSU and the negative regulatory role of this receptor
• in contrast, mutant bone marrow cells produce normal dose-dependent amounts of ROS upon dectin-1 triggered Syk activation after zymosan or curdlan treatment, which do not bind to Clec12a
|
