Phenotypes Associated with This Genotype

Genotype
MGI:5644329

• Allelic Composition: Chordc1^tm1Mbra/Chordc1⁺
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

premature death ( J:222040 )

• 60% of mice show rapid weight loss, hunched posture, and severe hypokinesia and die after 12 months of age

cellular

abnormal centrosome morphology ( J:222040 )

• increase in the number of bone marrow cells with more than 2 centrosomes

growth/size/body

weight loss ( J:222040 )

• 60% of mice show rapid weight loss from 12 months of age onward

enlarged liver ( J:222040 )

• hepatomegaly in diseased mice

enlarged spleen ( J:222040 )

behavior/neurological

hunched posture ( J:222040 )

• diseaed mice show hunched posture from 12 months of age onward

bradykinesia ( J:222040 )

• diseased mice develop hypokinesia from 12 months of age onward

hematopoietic system

abnormal myelopoiesis ( J:222040 )

• presence of immature myeloid cells in peripheral blood

anemia ( J:222040 )

abnormal bone marrow cell morphology/development ( J:222040 )

• increase in the number of bone marrow cells with more than 2 centrosomes

• number of aberrant metaphases is increased in the bone marrow

• bone marrow from mutants treated with fasudil, a ROCK inhibitor, induces apoptosis

decreased hemoglobin content ( J:222040 )

• in diseased mutants

increased nucleated erythrocyte cell number ( J:222040 )

• diseased mice show circulating nucleated red blood cells

anisocytosis ( J:222040 )

increased leukocyte cell number ( J:222040 )

• in diseased mutants

increased myeloid cell number ( J:222040 )

• dramatic expansion of the myeloid compartment in different organs

• 50% of diseased mice show the presence of myeloid infiltrations in the liver

• however, expansion of monocytes and eosinophils is not seen

increased myeloid cell number in bone marrow ( J:222040 )

• bone marrow of diseased mice shows expansion of Mac-1+ Gr-1+ and Mac-1+ c-Kit- cells and a reduction of B220+ cells, indicating expansion of the myeloid population and reduction of the lymphoid compartment

reticulocytosis ( J:222040 )

abnormal spleen morphology ( J:222040 )

• increase of Mac-1+ Gr-1+ and Mac-1+ c-Kit- cells paralleled by a reduction in CD3+ cells in the spleen

enlarged spleen ( J:222040 )

immune system

abnormal myelopoiesis ( J:222040 )

• presence of immature myeloid cells in peripheral blood

increased leukocyte cell number ( J:222040 )

• in diseased mutants

abnormal spleen morphology ( J:222040 )

• increase of Mac-1+ Gr-1+ and Mac-1+ c-Kit- cells paralleled by a reduction in CD3+ cells in the spleen

enlarged spleen ( J:222040 )

liver/biliary system

enlarged liver ( J:222040 )

• hepatomegaly in diseased mice

neoplasm

increased chronic myelocytic leukemia incidence ( J:222040 )

• with age, mice develop a fatal Philadelphia-negative myeloproliferative disease resembling atypical chronic myeloid leukemia

• two diseased mutants show the presence of a pool of Mac-1- c-Kit+ cells in peripheral blood, suggesting evolution of myleoproliferative disease into blast crisis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:222040