Phenotypes Associated with This Genotype

Genotype
MGI:5296515

• Allelic Composition: Sh2b3^tm1Paw/Sh2b3^tm1Paw
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

Sh2b3^tm1Paw/Sh2b3^tm1Paw mice develop a chronic myeloid leukemia-like myeloproliferative disease

hematopoietic system

enlarged spleen ( J:161643 )

• splenomegaly in older mutants is more pronounced than in young mutants, with a disproportionate expansion of myeloid cells

myeloid hyperplasia ( J:161643 )

• myeloid cells are expanded in peripheral blood, bone marrow, and spleen and infiltrate into livers

• 5-6-fold increase in percentage of Mac-1⁺Gr-1⁺ myeloid cells in the spleen

• older mutants (12-18 months of age) exhibit a 5-fold increase in myeloid cells compared to young mutants and a 9-fold increase compared to older wild-type mice

extramedullary hematopoiesis ( J:161643 )

• spleens of older mutants exhibit extramedullary hematopoiesis with disruption of the normal splenic architecture, due to infiltration of mature myeloid cells into the red pulp along with increased numbers of megakaryocytes

thrombocytosis ( J:161643 )

• 2 month old mutants exhibit a 3-fold increase in platelets

• platelet counts in older mutants remain unchanged compared to young mutants, but are elevated compared to wild-type mice

decreased B cell number ( J:161643 )

• reduction in B cells in the spleen

increased leukocyte cell number ( J:161643 )

• 2 month old mutants exhibit a 3-fold increase in white blood cells and older mice show an even greater elevation

increased granulocyte number ( J:161643 )

• bone marrow of aged mice exhibits increased numbers of granulocytic and monocytic cells

increased neutrophil cell number ( J:161643 )

• older mutants exhibit an increase in neutrophils

increased lymphocyte cell number ( J:161643 )

• older mutants exhibit a 1.7-fold increase in lymphocyte counts compared to younger mutants

increased monocyte cell number ( J:161643 )

• older mutants exhibit an increase in monocytes

immune system

enlarged spleen ( J:161643 )

• splenomegaly in older mutants is more pronounced than in young mutants, with a disproportionate expansion of myeloid cells

myeloid hyperplasia ( J:161643 )

• myeloid cells are expanded in peripheral blood, bone marrow, and spleen and infiltrate into livers

• 5-6-fold increase in percentage of Mac-1⁺Gr-1⁺ myeloid cells in the spleen

• older mutants (12-18 months of age) exhibit a 5-fold increase in myeloid cells compared to young mutants and a 9-fold increase compared to older wild-type mice

decreased B cell number ( J:161643 )

• reduction in B cells in the spleen

increased leukocyte cell number ( J:161643 )

• 2 month old mutants exhibit a 3-fold increase in white blood cells and older mice show an even greater elevation

increased granulocyte number ( J:161643 )

• bone marrow of aged mice exhibits increased numbers of granulocytic and monocytic cells

increased neutrophil cell number ( J:161643 )

• older mutants exhibit an increase in neutrophils

increased lymphocyte cell number ( J:161643 )

• older mutants exhibit a 1.7-fold increase in lymphocyte counts compared to younger mutants

increased monocyte cell number ( J:161643 )

• older mutants exhibit an increase in monocytes

growth/size/body

enlarged spleen ( J:161643 )

• splenomegaly in older mutants is more pronounced than in young mutants, with a disproportionate expansion of myeloid cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:161643