Analysis Tools
hematopoietic system
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• despite myeloid hyperplasia of the marrow, homozygotes are not anemic, contain normal amounts of erythrocytes and hemoglobin, a normal hematocrit value, and do not display an increase in nucleated red blood cells
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• mutant neutrophils show a normal locomotor function and are effective at intracellular and extracellular killing of bacteria
• however, mutant neutrophils fail to chemotax in response to CXCL2 (MIP-2), and show impaired migration in response to thioglycollate injection; the number of mutant neutrophils that migrates to the peritoneum is one-fifth that of wild-type
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• at necropsy, all homozygotes display a 2-4-fold increase in spleen size relative to wild-type
• in contrast, the thymus and all other organs remain grossly normal
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• the presence of metamyelocytes, bands and neutrophils in normal ratios suggests that extramedullary myelopoiesis occurs in the liver, lymph node and spleen
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• ~25% of homozygotes display multiple foci of granulopoiesis in the periportal region of the liver
• however, no signs of parenchymal infiltration, inflammation or hepatic damage are observed
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• homozygotes show a significant increase in bone marrow cellularity composed of the normal myeloid maturation series; the erythroid series remains unchanged
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• homozygotes show a ~12-fold increase in circulating neutrophils relative to wild-type
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• homozygotes display a ~10-fold increase in B cells relative to wild-type mice
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• spenomegaly results from expansion of the splenic white pulp by proliferation of myeloid elements (metamyelocytes, bands and neutrophils) and megakaryocytes
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immune system
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• mutant neutrophils show a normal locomotor function and are effective at intracellular and extracellular killing of bacteria
• however, mutant neutrophils fail to chemotax in response to CXCL2 (MIP-2), and show impaired migration in response to thioglycollate injection; the number of mutant neutrophils that migrates to the peritoneum is one-fifth that of wild-type
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• at necropsy, all homozygotes display a 2-4-fold increase in spleen size relative to wild-type
• in contrast, the thymus and all other organs remain grossly normal
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• the presence of metamyelocytes, bands and neutrophils in normal ratios suggests that extramedullary myelopoiesis occurs in the liver, lymph node and spleen
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• ~25% of homozygotes display multiple foci of granulopoiesis in the periportal region of the liver
• however, no signs of parenchymal infiltration, inflammation or hepatic damage are observed
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• homozygotes show a significant increase in bone marrow cellularity composed of the normal myeloid maturation series; the erythroid series remains unchanged
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• homozygotes show a ~12-fold increase in circulating neutrophils relative to wild-type
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• homozygotes display a ~10-fold increase in B cells relative to wild-type mice
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• spenomegaly results from expansion of the splenic white pulp by proliferation of myeloid elements (metamyelocytes, bands and neutrophils) and megakaryocytes
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• homozygotes display significantly high serum levels of IL-6 (average of 4.8 ng/ml) relative to wild-type mice (below 0.1 ng/ml)
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• in lymph nodes, the medullary cords are expanded by multiple foci of myelopoiesis, Russell bodies, and plasma cells, compressing the adjacent medullary sinuses
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• most mutant lymph nodes are enlarged; however, the degree of enlargement varies among individual mice
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• all homozygotes exhibit enlarged cervical lymph nodes (3- to 10-fold)
• in contrast, mutant inguinal and popliteal lymph nodes appear grossly normal
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skeleton
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• in homozygotes, the femur and tibia exhibit a grossly white marrow as opposed to the normal red marrow found in wild-type
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homeostasis/metabolism
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• homozygotes display significantly high serum levels of IL-6 (average of 4.8 ng/ml) relative to wild-type mice (below 0.1 ng/ml)
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cellular
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• ~25% of homozygotes display multiple foci of granulopoiesis in the periportal region of the liver
• however, no signs of parenchymal infiltration, inflammation or hepatic damage are observed
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• mutant neutrophils show a normal locomotor function and are effective at intracellular and extracellular killing of bacteria
• however, mutant neutrophils fail to chemotax in response to CXCL2 (MIP-2), and show impaired migration in response to thioglycollate injection; the number of mutant neutrophils that migrates to the peritoneum is one-fifth that of wild-type
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growth/size/body
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• at necropsy, all homozygotes display a 2-4-fold increase in spleen size relative to wild-type
• in contrast, the thymus and all other organs remain grossly normal
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