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Phenotypes Associated with This Genotype
Genotype
MGI:3575736
Allelic
Composition
Sipa1tm1Nm/Sipa1tm1Nm
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Sipa1tm1Nm mutation (0 available); any Sipa1 mutation (21 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• around 1 year of age 14 out of 60 mutants develop chronic myelocytic leukemia in the chronic phase and 35 out of 60 develop chronic myelocytic leukemia in blast crisis with extensive infiltration of the bone marrow and other vital organs
• blast cells are of various lineages including myeloid, erythroid, B and mixed lineages but not of the T lineage
• 95% of homozygotes develop myeloid disorders by 16 months of age

hematopoietic system
• the frequency of committed hematopoietic progenitors of all lineages is increased and in particular progenitors of macrophages in the bone marrow and erythroid and mixed progenitors in the spleen
• significant numbers of committed hematopoietic progenitor cells are found in the circulation in homozygotes
• at about 1 year of age 14 out of 60 have extramedullary hematopoiesis
• around 1 year of age some homozygotes develop severe anemia with less than 6 x 106 RBC/mm3
• at about 1 year of age 14 out of 60 have pale, hyper cellular bone marrow containing mostly mature myeloid cells and reduced erythroid cells numbers
• 8 out of 60 mutants display mosaic hyperplatic and hypoplastic regions in the bone marrow
• total nucleated cell numbers in the bone marrow are increased 1.5- to 2-fold compared to wild-type mice
• around 1 year of age some homozygotes develop leukocytosis with over 40 x 103 cells/mm3
• 35 out of 60 mutants display peripheral leukocytosis with varying proportions (from 14% to 85%) of blast cells
• at about 1 year of age 14 out of 60 have increased peripheral blood leuokocytes that are mostly mature granulocytes with few blast cells
• at about 1 year of age 8 out of 60 display pancytopenia with dysplastic granulocytes, large mono- or binuclear megakaryocytic cells and some blastic cells in the peripheral blood
• hematopoietic stem cells are increased in the bone marrow by 3 months with progressive increases seen by 8 months
• at about 1 year of age 14 out of 60 have marked splenomegaly
• total nucleated cell numbers in the spleen are increased 50-fold compared to wild-type mice

immune system
• around 1 year of age some homozygotes develop leukocytosis with over 40 x 103 cells/mm3
• 35 out of 60 mutants display peripheral leukocytosis with varying proportions (from 14% to 85%) of blast cells
• at about 1 year of age 14 out of 60 have increased peripheral blood leuokocytes that are mostly mature granulocytes with few blast cells
• at about 1 year of age 14 out of 60 have marked splenomegaly
• total nucleated cell numbers in the spleen are increased 50-fold compared to wild-type mice

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
chronic myeloid leukemia DOID:8552 OMIM:608232
J:97239


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
03/13/2019
MGI 6.13
The Jackson Laboratory