Analysis Tools
hematopoietic system
|
• neutrophils have reduced rates of chemotaxis to MIP-2 in transwell assays
• reduced motility is attributable to perturbed actin depolymerization kinetics
|
|
• erythropoiesis is decreased in the bone marrow but increased in the spleen
|
|
• granulopoiesis is expanded in the bone marrow and spleen
|
|
• there are striking morphological abnormalities including an immature, malformed demarcation membrane system (DMS), aberrant granule distribution, and large cytoplasmic regions that were entirely devoid of both DMS and granules
|
|
• there is a 4-fold increase in nucleated megakaryocytes found in the spleen with a modest increase observed in the bone marrow
|
|
• the numbers of neutrophils in the blood are elevated by 7 weeks of age with larger numbers observed in mice 14 weeks of age
• there is a significant positive correlation between the severity of inflammatory lesions and the number of neutrophils found in the blood
|
|
• platelets show severe morphologic abnormalities including increased size, loss of discoid shape, and irregular distribution of granules and microtubule coil
|
|
• the rate at which new platelets appear in circulation is significantly lower than in wild-type mice while the rate they are cleared from the blood remains the same
• abnormal enucleated megakaryocyte cytoplasm was found throughout the spleen and bone marrow indicating a breakdown in the platelet shedding process
|
|
• aberrant distribution of alpha-granules
|
|
• mice exhibit platelet levels that are only 20% of wild-type levels at both 7 weeks and 14 months of age
|
|
• aberrant distribution of dense bodies
|
|
• loss of discoid shape
|
|
• mice exhibit an increase in mean platelet volume
|
|
• there is increased numbers of osteoclasts in the bones of the limbs and paws that is associated with inflammatory lesions
|
|
• the inflammatory lesions increase osteoclast activity in the bones of the limbs and paws that leads to bone damage
|
homeostasis/metabolism
|
• there is a significant increase in time to cessation of bleeding after tail clipping
• wild-type mice stop bleeding on average 3.9 minutes after tail clipping while mutant mice all bled for 10 minutes at which time they were cauterized
|
immune system
|
• neutrophils have reduced rates of chemotaxis to MIP-2 in transwell assays
• reduced motility is attributable to perturbed actin depolymerization kinetics
|
|
• spontaneous inflammatory lesions occur on the outside portions of the ear by 6 months of age
|
|
• granulopoiesis is expanded in the bone marrow and spleen
|
|
• the rate at which new platelets appear in circulation is significantly lower than in wild-type mice while the rate they are cleared from the blood remains the same
• abnormal enucleated megakaryocyte cytoplasm was found throughout the spleen and bone marrow indicating a breakdown in the platelet shedding process
|
|
• the numbers of neutrophils in the blood are elevated by 7 weeks of age with larger numbers observed in mice 14 weeks of age
• there is a significant positive correlation between the severity of inflammatory lesions and the number of neutrophils found in the blood
|
|
• there is increased numbers of osteoclasts in the bones of the limbs and paws that is associated with inflammatory lesions
|
|
• the inflammatory lesions increase osteoclast activity in the bones of the limbs and paws that leads to bone damage
|
|
• spontaneous inflammatory lesions first occur on the tail
• lesions progress over time to include the limbs and the paws
• lesions are characterized by leukocytic infiltration, necrosis of tissue and cartilage destruction
|
hearing/vestibular/ear
|
• spontaneous inflammatory lesions occur on the outside portions of the ear by 6 months of age
|
skeleton
|
• there is increased numbers of osteoclasts in the bones of the limbs and paws that is associated with inflammatory lesions
|
|
• the inflammatory lesions increase osteoclast activity in the bones of the limbs and paws that leads to bone damage
|
integument
|
• spontaneous inflammatory lesions first occur on the tail
• lesions progress over time to include the limbs and the paws
• lesions are characterized by leukocytic infiltration, necrosis of tissue and cartilage destruction
|
|
• epidermal hyperplasia occurs at sites of inflammatory lesions
|
cellular
|
• neutrophils have reduced rates of chemotaxis to MIP-2 in transwell assays
• reduced motility is attributable to perturbed actin depolymerization kinetics
|
