Phenotypes associated with this allele

• Allele Symbol: Gata1^tm2Sho
• Allele Name: targeted mutation 2, Stuart Orkin
• Allele ID: MGI:2177586
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gata1^tm2Sho/Gata1^tm2Sho	involves: 129S4/SvJae	MGI:3798925
hm2	Gata1^tm2Sho/Gata1^tm2Sho	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:2653501
ht3	Gata1^tm2Sho/Gata1^+	involves: 129S4/SvJae * C57BL/6	MGI:4415825
ot4	Gata1^tm2Sho/Y	involves: 129S4/SvJae * C57BL/6	MGI:4415824
ot5	Gata1^tm2Sho/Y	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:4417827

Genotype
MGI:3798925

hm1

• Allelic Composition: Gata1^tm2Sho/Gata1^tm2Sho
• Genetic Background: involves: 129S4/SvJae

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

skeleton

increased osteoclast cell number ( J:111270 )

♀ • the number of osteoclasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoblasts

increased compact bone volume ( J:111270 )

♀ • at 5 to 9 months of age, the cortical bone is increased 2- to 3-fold compared to in wild-type mice

increased trabecular bone volume ( J:111270 )

♀ • trabecular bone volume for the entire medullary canal is increased 150-fold compared to in wild-type mice

♀ • at 5 to 9 months of age, the trabecular bone is increased 2- to 3-fold compared to in wild-type mice

♀ • at 5 months, the diaphyseal shafts are occluded with bone unlike in wild-type mice

increased osteoblast cell number ( J:111270 )

♀ • the number of osteoblasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoclasts

♀ • osteoblast proliferation is increased up to 6-fold when cultured with megakaryocytes compared to in wild-type mice

increased bone ossification ( J:111270 )

♀ • bone formation is increased 2.7-fold compared to in wild-type mice

hematopoietic system

increased osteoclast cell number ( J:111270 )

♀ • the number of osteoclasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoblasts

immune system

increased osteoclast cell number ( J:111270 )

♀ • the number of osteoclasts is increased by greater than 3-fold compared to in wild-type mice and is accompanied by a proportional increase in osteoblasts

Genotype
MGI:2653501

hm2

• Allelic Composition: Gata1^tm2Sho/Gata1^tm2Sho
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

hematopoietic system

abnormal definitive hematopoiesis ( J:78348 )

♀ • no sign of active hemopoiesis is seen in the liver of mutants after birth (1-12 months of age), however by 18 months of age, foci of hematopoiesis are seen in the liver parenchyma

abnormal common myeloid progenitor cell morphology ( J:78348 , J:78540 )

♀ • number of myeloid progenitor cells (CFU-GM) circulating in the blood increases by 2- to 10-fold at 8-12 months of age and remain higher than normal after this time (J:78348)

♀ • spleen and marrow contains increased numbers of megakaryocytic and bipotent (erythroid/megakaryocytic) precursors (J:78540)

extramedullary hematopoiesis ( J:78540 )

♀ • transition of the major hematopoietic site from the marrow to the spleen

anemia ( J:78348 )

♀ • mutants become anemic from 15 months of age

decreased bone marrow cell number ( J:78348 , J:78540 )

♀ • total marrow cellularity is reduced already at 4-8 months of age and further reduced by 2-fold at 15-20 months of age (J:78348)

♀ • 2- to 3-fold decrease in the frequency of all types of progenitor cells in the bone marrow with age; when adjusted for the reduction in total marrow cellularity, corresponds to a 4-fold reduction in total number of progenitor cells per femur (J:78348)

♀ • bone marrow contains 3 times fewer cells than wild-type (J:78540)

abnormal erythroid progenitor cell morphology ( J:78348 , J:78540 )

♀ • erythroid progenitors (BFU-E, CFU-E) in the spleen, though higher than in wild-type mice, decrease 2- to 3-fold over time in mutants (J:78348)

♀ (J:78540)

decreased erythroid progenitor cell number ( J:78540 )

♀ • overall erythroid precursor cell content in the marrow is lower than in wild-type

increased erythroid progenitor cell number ( J:78348 , J:78540 )

♀ • number of erythroid progenitor cells (CFU-E and BFU-E) circulating in the blood increases by 2- to 10-fold at 8-12 months of age and remain higher than normal after this time (J:78348)

♀ • marrow and spleen contain a higher frequency of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E) derived colonies (J:78540)

♀ • spleen contains 7-20-fold higher numbers of erythroid precursors and bipotent (erythroid/megakaryocytic) precursors (J:78540)

♀ • phenylhydrazine (PHZ) treated mutants exhibit an increase in CFU-E (J:78540)

♀ • erythropoietin (EPO) treated mutants exhibit an increase in both early (BFU-E) and late (CFU-E) progenitor cells in the marrow and spleen (J:78540)

abnormal megakaryocyte progenitor cell morphology ( J:78348 )

♀ • number of megakaryocyte progenitor cells (CFU-Mk) circulating in the blood increases by 18-20 months of age

♀ • frequency of megakaryocytic progenitors (CFU-Mkp and CFU-Mkm) in the spleen, which are already higher at 4-8 months of age, further increases at 15-20 months

♀ • however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age

decreased erythrocyte cell number ( J:78348 )

♀ • number of circulating red cells is decreased at 15-20 months of age

abnormal hematocrit ( J:78540 )

♀ • mutants exhibit an accelerated hematocrit response to both acute (PHZ treatment) and chronic (EPO administration) erythroid stimulation which lasts longer than in wild-type

decreased hematocrit ( J:78348 )

♀ • at 15-20 months of age

increased number of Howell-Jolly bodies ( J:78348 )

♀ • erythrocytes with Howell-Jolly bodies are seen in the blood

poikilocytosis ( J:78348 )

♀ • tear-drop poikilocytes are seen in the blood

polychromatophilia ( J:78348 )

♀ • erythrocytes with polychromatophilia are seen in the blood

increased neutrophil cell number ( J:78348 )

♀ • progressive increase in the percentages of neutrophils by 15-20 months of age

thrombocytopenia ( J:78348 , J:78540 )

♀ (J:78348)

♀ • 10-fold decrease in platelet numbers (J:78540)

♀ • mutants are thrombocytopenic in response to phenylhydrazine (PHZ)-induced anemia or erythropoietin (EPO)-iduced polycythemia but have normal hematocrit levels (J:78540)

abnormal platelet shape ( J:78348 , J:78540 )

♀ (J:78348)

♀ • platelets appear abnormal and bigger than normal platelets (J:78540)

decreased lymphocyte cell number ( J:78348 )

♀ • progressive decrease in the percentage of lymphocytes

abnormal spleen morphology ( J:78348 )

♀ • accumulation of reticulin fibers with age in the spleen

♀ • while spleen size further increases with age, total spleen cellularity, though remaining significantly higher than in normal mice, decreases with age; total number of cells in the spleen is first reduced at 8-12 months of age

♀ • however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age

enlarged spleen ( J:78348 , J:78540 )

♀ • spleen size increases with age and at 15-20 months of age is due to an accumulation of collagen fibers (J:78348)

♀ • spleens are 2.5-fold larger (J:78540)

♀ • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls (J:78540)

abnormal spleen red pulp morphology ( J:78540 )

♀ • the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes

♀ • red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells

increased splenocyte number ( J:78540 )

♀ • spleen contains 3 times more cells than wild-type

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:78540 )

♀ • mutants recover 2 days faster from the PHZ-induced anemia than controls

immune system

increased neutrophil cell number ( J:78348 )

♀ • progressive increase in the percentages of neutrophils by 15-20 months of age

decreased lymphocyte cell number ( J:78348 )

♀ • progressive decrease in the percentage of lymphocytes

abnormal spleen morphology ( J:78348 )

♀ • accumulation of reticulin fibers with age in the spleen

♀ • while spleen size further increases with age, total spleen cellularity, though remaining significantly higher than in normal mice, decreases with age; total number of cells in the spleen is first reduced at 8-12 months of age

♀ • however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age

enlarged spleen ( J:78348 , J:78540 )

♀ • spleen size increases with age and at 15-20 months of age is due to an accumulation of collagen fibers (J:78348)

♀ • spleens are 2.5-fold larger (J:78540)

♀ • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls (J:78540)

abnormal spleen red pulp morphology ( J:78540 )

♀ • the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes

♀ • red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells

increased splenocyte number ( J:78540 )

♀ • spleen contains 3 times more cells than wild-type

skeleton

abnormal bone marrow morphology ( J:78348 , J:78540 )

♀ • starting at 12 months of age, a progressive reduction of the space available in the bone marrow for hemopoietic cells due to the simultaneous increase of bone trabeculae and intracellular matrix (J:78348)

♀ • progressive accumulation of fibers in the intercellular space of the marrow; the fibers change from fine and diffuse reticulin fibers at 6 months of age to gross collagen fibers from 12 months on and almost completely fills the femoral cavity (J:78348)

♀ • bone marrow contains larger-than-normal red cells and apoptotic cells (J:78540)

myelofibrosis ( J:78348 )

♀ • myelofibrotic degeneration of the marrow and spleen with age; about 7 times more megakaryocytes in the bone marrow than controls

♀ • expression of growth factor genes implicated in the development of myelofibrosis is increased in the marrow

♀ • presence of tear-drop poikilocytes and progenitor cells in the blood, collagen fibers in the marrow and in the spleen and hemopoietic foci in the liver, all markers of myelofibrosis

increased bone trabecula number ( J:78348 )

♀ • starting at 12 months of age, an increase of bone trabeculae is seen in the bone marrow

increased bone ossification ( J:78348 )

♀ • in the oldest mice, increased osteogenesis eventually occludes the femoral cavity

liver/biliary system

abnormal liver morphology ( J:78348 )

♀ • starting from 8-12 months of age, significant numbers of progenitor cells are seen in the liver that increases further at 15-20 months of age

mortality/aging

premature death ( J:78348 )

♀ • most mutants die between 14 and 20 months of age, and only 9 survive past 20 months of age

postnatal lethality, incomplete penetrance ( J:78348 )

♀ • 9 of 178 mutants born alive die within the first 15 days of life

prenatal lethality, incomplete penetrance ( J:78348 )

♀ • only 30% of pregnancies induced result in viable pups

growth/size/body

enlarged spleen ( J:78348 , J:78540 )

♀ • spleen size increases with age and at 15-20 months of age is due to an accumulation of collagen fibers (J:78348)

♀ • spleens are 2.5-fold larger (J:78540)

♀ • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls (J:78540)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelofibrosis		DOID:4971	OMIM:254450	J:78348

Genotype
MGI:4415825

ht3

• Allelic Composition: Gata1^tm2Sho/Gata1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

hematopoietic system

abnormal megakaryocyte differentiation ( J:41605 )

♀

increased megakaryocyte cell number ( J:41605 )

♀ • large increase in megakaryocytes in hematopoietic tissues, presumably because of mosaicism resulting from random X inactivation

♀ • excess of abnormal megakaryocytes in the yolk sac and early fetal liver

♀ • however, normal numbers of platelets

abnormal megakaryocyte progenitor cell morphology ( J:41605 )

♀ • proliferation of megakaryocyte progenitors is greatly enhanced in fetal livers, presumably because of mosaicism resulting from random X inactivation

cellular

abnormal megakaryocyte differentiation ( J:41605 )

♀

Genotype
MGI:4415824

ot4

• Allelic Composition: Gata1^tm2Sho/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

decreased survivor rate ( J:41605 )

♂ • 5% of males survive fetal anemia into adult life

hematopoietic system

anemia ( J:41605 )

♂

abnormal megakaryocyte morphology ( J:41605 )

♂ • megakaryocytes are smaller than normal, have scant cytoplasm and condensed nuclei

abnormal megakaryocyte differentiation ( J:41605 )

♂ • maturation of megakaryocytes is arrested

increased megakaryocyte cell number ( J:41605 )

♂ • 100-fold increase in megakaryocytes in the spleen and bone marrow

♂ • excess of abnormal megakaryocytes in the yolk sac and early fetal liver

abnormal megakaryocyte progenitor cell morphology ( J:41605 )

♂ • proliferation of megakaryocyte progenitors is greatly enhanced in fetal livers

thrombocytopenia ( J:41605 )

♂ • platelet numbers are reduced to about 15% of normal

increased mean platelet volume ( J:41605 )

♂

cellular

abnormal megakaryocyte differentiation ( J:41605 )

♂ • maturation of megakaryocytes is arrested

Genotype
MGI:4417827

ot5

• Allelic Composition: Gata1^tm2Sho/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

hematopoietic system

abnormal definitive hematopoiesis ( J:78348 )

♂ • no sign of active hemopoiesis is seen in the liver of mutants after birth (1-12 months of age), however by 18 months of age, foci of hematopoiesis are seen in the liver parenchyma

abnormal common myeloid progenitor cell morphology ( J:78348 , J:78540 )

♂ • number of myeloid progenitor cells (CFU-GM) circulating in the blood increases by 2- to 10-fold at 8-12 months of age and remain higher than normal after this time (J:78348)

♂ • spleen and marrow contains increased numbers of megakaryocytic and bipotent (erythroid/megakaryocytic) precursors (J:78540)

extramedullary hematopoiesis ( J:78540 )

♂ • transition of the major hematopoietic site from the marrow to the spleen

anemia ( J:78348 )

♂ • mutants become anemic from 15 months of age

decreased bone marrow cell number ( J:78348 , J:78540 )

♂ • total marrow cellularity is reduced already at 4-8 months of age and further reduced by 2-fold at 15-20 months of age (J:78348)

♂ • 2- to 3-fold decrease in the frequency of all types of progenitor cells in the bone marrow with age; when adjusted for the reduction in total marrow cellularity, corresponds to a 4-fold reduction in total number of progenitor cells per femur (J:78348)

♂ • bone marrow contains 3 times fewer cells than wild-type (J:78540)

abnormal erythroid progenitor cell morphology ( J:78348 , J:78540 )

♂ • erythroid progenitors (BFU-E, CFU-E) in the spleen, though higher than in wild-type mice, decrease 2- to 3-fold over time in mutants (J:78348)

♂ (J:78540)

decreased erythroid progenitor cell number ( J:78540 )

♂ • overall erythroid precursor cell content in the marrow is lower than in wild-type

increased erythroid progenitor cell number ( J:78348 , J:78540 )

♂ • number of erythroid progenitor cells (CFU-E and BFU-E) circulating in the blood increases by 2- to 10-fold at 8-12 months of age and remain higher than normal after this time (J:78348)

♂ • marrow and spleen contain a higher frequency of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E) derived colonies (J:78540)

♂ • spleen contains 7-20-fold higher numbers of erythroid precursors and bipotent (erythroid/megakaryocytic) precursors (J:78540)

♂ • phenylhydrazine (PHZ) treated mutants exhibit an increase in CFU-E (J:78540)

♂ • erythropoietin (EPO) treated mutants exhibit an increase in both early (BFU-E) and late (CFU-E) progenitor cells in the marrow and spleen (J:78540)

abnormal megakaryocyte progenitor cell morphology ( J:78348 )

♂ • number of megakaryocyte progenitor cells (CFU-Mk) circulating in the blood increases by 18-20 months of age

♂ • frequency of megakaryocytic progenitors (CFU-Mkp and CFU-Mkm) in the spleen, which are already higher at 4-8 months of age, further increases at 15-20 months

♂ • however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age

decreased erythrocyte cell number ( J:78348 )

♂ • number of circulating red cells is decreased at 15-20 months of age

abnormal hematocrit ( J:78540 )

♂ • mutants exhibit an accelerated hematocrit response to both acute (PHZ treatment) and chronic (EPO administration) erythroid stimulation which lasts longer than in wild-type

decreased hematocrit ( J:78348 )

♂ • at 15-20 months of age

increased number of Howell-Jolly bodies ( J:78348 )

♂ • erythrocytes with Howell-Jolly bodies are seen in the blood

poikilocytosis ( J:78348 )

♂ • tear-drop poikilocytes are seen in the blood

polychromatophilia ( J:78348 )

♂ • erythrocytes with polychromatophilia are seen in the blood

increased neutrophil cell number ( J:78348 )

♂ • progressive increase in the percentages of neutrophils by 15-20 months of age

thrombocytopenia ( J:78348 , J:78540 )

♂ (J:78348)

♂ • 10-fold decrease in platelet numbers (J:78540)

♂ • mutants are thrombocytopenic in response to phenylhydrazine (PHZ)-induced anemia or erythropoietin (EPO)-iduced polycythemia but have normal hematocrit levels (J:78540)

abnormal platelet shape ( J:78348 , J:78540 )

♂ (J:78348)

♂ • platelets appear abnormal and bigger than normal platelets (J:78540)

decreased lymphocyte cell number ( J:78348 )

♂ • progressive decrease in the percentage of lymphocytes

abnormal spleen morphology ( J:78348 )

♂ • accumulation of reticulin fibers with age in the spleen

♂ • while spleen size further increases with age, total spleen cellularity, though remaining significantly higher than in normal mice, decreases with age; total number of cells in the spleen is first reduced at 8-12 months of age

♂ • however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age

enlarged spleen ( J:78348 , J:78540 )

♂ • spleen size increases with age and at 15-20 months of age is due to an accumulation of collagen fibers (J:78348)

♂ • spleens are 2.5-fold larger (J:78540)

♂ • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls (J:78540)

abnormal spleen red pulp morphology ( J:78540 )

♂ • the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes

♂ • red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells

increased splenocyte number ( J:78540 )

♂ • spleen contains 3 times more cells than wild-type

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:78540 )

♂ • mutants recover 2 days faster from the PHZ-induced anemia than controls

immune system

increased neutrophil cell number ( J:78348 )

♂ • progressive increase in the percentages of neutrophils by 15-20 months of age

decreased lymphocyte cell number ( J:78348 )

♂ • progressive decrease in the percentage of lymphocytes

abnormal spleen morphology ( J:78348 )

♂ • accumulation of reticulin fibers with age in the spleen

♂ • while spleen size further increases with age, total spleen cellularity, though remaining significantly higher than in normal mice, decreases with age; total number of cells in the spleen is first reduced at 8-12 months of age

♂ • however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age

enlarged spleen ( J:78348 , J:78540 )

♂ • spleen size increases with age and at 15-20 months of age is due to an accumulation of collagen fibers (J:78348)

♂ • spleens are 2.5-fold larger (J:78540)

♂ • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls (J:78540)

abnormal spleen red pulp morphology ( J:78540 )

♂ • the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes

♂ • red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells

increased splenocyte number ( J:78540 )

♂ • spleen contains 3 times more cells than wild-type

skeleton

abnormal bone marrow morphology ( J:78348 , J:78540 )

♂ • starting at 12 months of age, a progressive reduction of the space available in the bone marrow for hemopoietic cells due to the simultaneous increase of bone trabeculae and intracellular matrix (J:78348)

♂ • progressive accumulation of fibers in the intercellular space of the marrow; the fibers change from fine and diffuse reticulin fibers at 6 months of age to gross collagen fibers from 12 months on and almost completely fills the femoral cavity (J:78348)

♂ • bone marrow contains larger-than-normal red cells and apoptotic cells (J:78540)

myelofibrosis ( J:78348 )

♂ • myelofibrotic degeneration of the marrow and spleen with age; about 7 times more megakaryocytes in the bone marrow than controls

♂ • expression of growth factor genes implicated in the development of myelofibrosis is increased in the marrow

♂ • presence of tear-drop poikilocytes and progenitor cells in the blood, collagen fibers in the marrow and in the spleen and hemopoietic foci in the liver, all markers of myelofibrosis

increased bone trabecula number ( J:78348 )

♂ • starting at 12 months of age, an increase of bone trabeculae is seen in the bone marrow

increased bone ossification ( J:78348 )

♂ • in the oldest mice, increased osteogenesis eventually occludes the femoral cavity

liver/biliary system

abnormal liver morphology ( J:78348 )

♂ • no sign of active hemopoiesis is seen in the liver of mutants after birth (1-12 months of age), however by 18 months of age, foci of hematopoiesis are seen in the liver parenchyma

mortality/aging

premature death ( J:78348 )

♂ • most mutants die between 14 and 20 months of age, and only 9 survive past 20 months of age

postnatal lethality, incomplete penetrance ( J:78348 )

♂ • 9 of 178 mutants born alive die within the first 15 days of life

prenatal lethality, incomplete penetrance ( J:78348 )

♂ • only 30% of pregnancies induced result in viable pups

growth/size/body

enlarged spleen ( J:78348 , J:78540 )

♂ • spleen size increases with age and at 15-20 months of age is due to an accumulation of collagen fibers (J:78348)

♂ • spleens are 2.5-fold larger (J:78540)

♂ • spleens of PHZ-and EPO-treated mutants are bigger and contain more cells than treated controls (J:78540)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelofibrosis		DOID:4971	OMIM:254450	J:78348