Phenotypes associated with this allele

• Allele Symbol: Sh2b3^tm1Paw
• Allele Name: targeted mutation 1, Tony Pawson
• Allele ID: MGI:2383957
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sh2b3^tm1Paw/Sh2b3^tm1Paw	B6.129-Sh2b3^tm1Paw	MGI:3621937
hm2	Sh2b3^tm1Paw/Sh2b3^tm1Paw	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:3621933
hm3	Sh2b3^tm1Paw/Sh2b3^tm1Paw	involves: 129S1/Sv * 129X1/SvJ	MGI:5296515

Genotype
MGI:3621937

hm1

• Allelic Composition: Sh2b3^tm1Paw/Sh2b3^tm1Paw
• Genetic Background: B6.129-Sh2b3^tm1Paw

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

hematopoietic system

spleen hyperplasia ( J:107464 )

• splenic BFU-e and CFU-e progenitors are increased by 3.2 and 4.6 fold compared to wild-type; mutants have 1.9x as many spleen cells in null mice

anemia ( J:107464 )

• null mice exhibit a less severe phenylhydrazine-induced anemia and faster recovery compared to wild-type

increased bone marrow cell number ( J:107464 )

• null mice have 30% more bone marrow cells than controls

increased erythroid progenitor cell number ( J:107464 )

• the earliest erythropoietic progenitors (burst forming units) are increased 1.7 fold in bone marrow compared to wild-type

immune system

spleen hyperplasia ( J:107464 )

• splenic BFU-e and CFU-e progenitors are increased by 3.2 and 4.6 fold compared to wild-type; mutants have 1.9x as many spleen cells in null mice

growth/size/body

spleen hyperplasia ( J:107464 )

• splenic BFU-e and CFU-e progenitors are increased by 3.2 and 4.6 fold compared to wild-type; mutants have 1.9x as many spleen cells in null mice

Genotype
MGI:3621933

hm2

• Allelic Composition: Sh2b3^tm1Paw/Sh2b3^tm1Paw
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

Primary splenomegaly and extramedullary hematopoiesis in Sh2b3^tm1Paw/Sh2b3^tm1Paw mice

cellular

abnormal granulocyte differentiation ( J:77248 )

• numbers of progenitor cells are decreased by 15%

abnormal monocyte differentiation ( J:77248 )

• numbers of progenitor cells are decreased by 15%

increased cell proliferation ( J:77248 )

• nutant splenic cells exhibit hypersensitive proliferation in response to SCF and Il-3

hematopoietic system

abnormal granulocyte differentiation ( J:77248 )

• numbers of progenitor cells are decreased by 15%

abnormal monocyte differentiation ( J:77248 )

• numbers of progenitor cells are decreased by 15%

enlarged spleen ( J:77248 )

• mutants exhibit splenomegaly compared to wild-type (0.195g vs. 0.062g respectively)

extramedullary hematopoiesis ( J:77248 )

• mutants have extensive extramedullary hematopoiesis in the spleen

abnormal megakaryocyte morphology ( J:77248 )

• increased numbers of megakaryocytes, as well as erythrocytes are apparent in the splenic red pulp

increased megakaryocyte cell number ( J:77248 )

• there is an increase in numbers of megakaryocytes in the bone marrow of mutants

thrombocytosis ( J:77248 )

• counts are increased in mutants

abnormal leukocyte cell number ( J:77248 )

• counts are markedly increased in mutants

increased B cell number ( J:77248 )

• bone marrow and spleens of mutants show a higher percentage of B220+ lymphocytes

spleen fibrosis ( J:77248 )

• mutants are characterized by fibrosis of the spleen

immune system

abnormal granulocyte differentiation ( J:77248 )

• numbers of progenitor cells are decreased by 15%

abnormal monocyte differentiation ( J:77248 )

• numbers of progenitor cells are decreased by 15%

enlarged spleen ( J:77248 )

• mutants exhibit splenomegaly compared to wild-type (0.195g vs. 0.062g respectively)

abnormal leukocyte cell number ( J:77248 )

• counts are markedly increased in mutants

increased B cell number ( J:77248 )

• bone marrow and spleens of mutants show a higher percentage of B220+ lymphocytes

spleen fibrosis ( J:77248 )

• mutants are characterized by fibrosis of the spleen

enlarged lymph nodes ( J:77248 )

• mutants have enlarged lymph nodes

growth/size/body

enlarged spleen ( J:77248 )

• mutants exhibit splenomegaly compared to wild-type (0.195g vs. 0.062g respectively)

Genotype
MGI:5296515

hm3

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

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