Phenotypes Associated with This Genotype

Genotype
MGI:3785507

• Allelic Composition: Wdr1^rede/Wdr1^rede
• Genetic Background: C57BL/6-Wdr1^rede

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

hematopoietic system

impaired neutrophil chemotaxis ( J:134092 )

• neutrophils have reduced rates of chemotaxis to MIP-2 in transwell assays

• reduced motility is attributable to perturbed actin depolymerization kinetics

abnormal erythropoiesis ( J:134092 )

• erythropoiesis is decreased in the bone marrow but increased in the spleen

abnormal myelopoiesis ( J:134092 )

• granulopoiesis is expanded in the bone marrow and spleen

anemia ( J:134092 )

• older mice are slightly anemic

abnormal megakaryocyte morphology ( J:134092 )

• 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

increased megakaryocyte cell number ( J:134092 )

• there is a 4-fold increase in nucleated megakaryocytes found in the spleen with a modest increase observed in the bone marrow

increased neutrophil cell number ( J:134092 )

• 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

abnormal platelet morphology ( J:134092 )

• platelets show severe morphologic abnormalities including increased size, loss of discoid shape, and irregular distribution of granules and microtubule coil

abnormal thrombopoiesis ( J:134092 )

• 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

abnormal platelet alpha-granule morphology ( J:134092 )

• aberrant distribution of alpha-granules

thrombocytopenia ( J:134092 )

• mice exhibit platelet levels that are only 20% of wild-type levels at both 7 weeks and 14 months of age

abnormal platelet dense granule morphology ( J:134092 )

• aberrant distribution of dense bodies

abnormal platelet shape ( J:134092 )

• loss of discoid shape

increased mean platelet volume ( J:134092 )

• mice exhibit an increase in mean platelet volume

increased osteoclast cell number ( J:134092 )

• there is increased numbers of osteoclasts in the bones of the limbs and paws that is associated with inflammatory lesions

abnormal osteoclast physiology ( J:134092 )

• the inflammatory lesions increase osteoclast activity in the bones of the limbs and paws that leads to bone damage

homeostasis/metabolism

increased bleeding time ( J:134092 )

• 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

impaired neutrophil chemotaxis ( J:134092 )

• neutrophils have reduced rates of chemotaxis to MIP-2 in transwell assays

• reduced motility is attributable to perturbed actin depolymerization kinetics

ear inflammation ( J:134092 )

• spontaneous inflammatory lesions occur on the outside portions of the ear by 6 months of age

abnormal myelopoiesis ( J:134092 )

• granulopoiesis is expanded in the bone marrow and spleen

abnormal thrombopoiesis ( J:134092 )

• 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

increased neutrophil cell number ( J:134092 )

• 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

increased osteoclast cell number ( J:134092 )

• there is increased numbers of osteoclasts in the bones of the limbs and paws that is associated with inflammatory lesions

abnormal osteoclast physiology ( J:134092 )

• the inflammatory lesions increase osteoclast activity in the bones of the limbs and paws that leads to bone damage

skin inflammation ( J:134092 )

• 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

ear inflammation ( J:134092 )

• spontaneous inflammatory lesions occur on the outside portions of the ear by 6 months of age

skeleton

increased osteoclast cell number ( J:134092 )

• there is increased numbers of osteoclasts in the bones of the limbs and paws that is associated with inflammatory lesions

abnormal osteoclast physiology ( J:134092 )

• the inflammatory lesions increase osteoclast activity in the bones of the limbs and paws that leads to bone damage

integument

skin inflammation ( J:134092 )

• 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 ( J:134092 )

• epidermal hyperplasia occurs at sites of inflammatory lesions

cellular

impaired neutrophil chemotaxis ( J:134092 )

• neutrophils have reduced rates of chemotaxis to MIP-2 in transwell assays

• reduced motility is attributable to perturbed actin depolymerization kinetics