Phenotypes associated with this allele

• Allele Symbol: Sipa1^tm1Nm
• Allele Name: targeted mutation 1, Nagahiro Minato
• Allele ID: MGI:3575291
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sipa1^tm1Nm/Sipa1^tm1Nm	involves: 129P2/OlaHsd * C57BL/6	MGI:3575736
ht2	Sipa1^tm1Nm/Sipa1^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3575737

Genotype
MGI:3575736

hm1

• Allelic Composition: Sipa1^tm1Nm/Sipa1^tm1Nm
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

neoplasm

increased chronic myelocytic leukemia incidence ( J:97239 )

• 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

enlarged spleen ( J:97239 )

• at about 1 year of age 14 out of 60 have marked splenomegaly

spleen hyperplasia ( J:97239 )

• total nucleated cell numbers in the spleen are increased 50-fold compared to wild-type mice

abnormal definitive hematopoiesis ( J:97239 )

• 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

extramedullary hematopoiesis ( J:97239 )

• at about 1 year of age 14 out of 60 have extramedullary hematopoiesis

anemia ( J:97239 )

• around 1 year of age some homozygotes develop severe anemia with less than 6 x 10⁶ RBC/mm³

abnormal bone marrow cell morphology/development ( J:97239 )

• 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

increased bone marrow cell number ( J:97239 )

• total nucleated cell numbers in the bone marrow are increased 1.5- to 2-fold compared to wild-type mice

increased leukocyte cell number ( J:97239 )

• 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

increased granulocyte number ( J:97239 )

• at about 1 year of age 14 out of 60 have increased peripheral blood leuokocytes that are mostly mature granulocytes with few blast cells

pancytopenia ( J:97239 )

• 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

increased hematopoietic stem cell number ( J:97239 )

• hematopoietic stem cells are increased in the bone marrow by 3 months with progressive increases seen by 8 months

immune system

enlarged spleen ( J:97239 )

• at about 1 year of age 14 out of 60 have marked splenomegaly

spleen hyperplasia ( J:97239 )

• total nucleated cell numbers in the spleen are increased 50-fold compared to wild-type mice

increased leukocyte cell number ( J:97239 )

• 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

increased granulocyte number ( J:97239 )

• at about 1 year of age 14 out of 60 have increased peripheral blood leuokocytes that are mostly mature granulocytes with few blast cells

growth/size/body

enlarged spleen ( J:97239 )

• at about 1 year of age 14 out of 60 have marked splenomegaly

spleen hyperplasia ( J:97239 )

• 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

Genotype
MGI:3575737

ht2

• Allelic Composition: Sipa1^tm1Nm/Sipa1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

neoplasm

increased chronic myelocytic leukemia incidence ( J:97239 )

• of the 15% (16 out of 102) of heterozygotes with increased WBC counts 4 had chronic myelocytic leukemia in the chronic phase and the other 12 were in blast crisis

hematopoietic system

enlarged spleen ( J:97239 )

• this 15% also had splenomegaly

decreased erythrocyte cell number ( J:97239 )

• 15% of heterozygotes have decreased RBC counts (6.35 +/- 0.6 x 10 ⁶ cells/mm³ compared to 9.32 +/- 0.04 x 10⁶ cells/mm³ in wild-type mice)

increased leukocyte cell number ( J:97239 )

• 15% of heterozygotes have increased mean WBC counts (22.3 +/- 5.8 x 10 ³ cells/mm³ compared to 8.7 +/- 10³ cells/mm³ in wild-type mice)

immune system

enlarged spleen ( J:97239 )

• this 15% also had splenomegaly

increased leukocyte cell number ( J:97239 )

• 15% of heterozygotes have increased mean WBC counts (22.3 +/- 5.8 x 10 ³ cells/mm³ compared to 8.7 +/- 10³ cells/mm³ in wild-type mice)

growth/size/body

enlarged spleen ( J:97239 )

• this 15% also had splenomegaly

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