Mouse Genome Informatics
hm
    Gata1tm2Sho/Gata1tm2Sho
involves: 129S4/SvJae * C57BL/6 * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
hematopoietic system
• 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 (J:78348)
• 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)
• number of circulating red cells is decreased at 15-20 months of age (J:78348)
• mutants exhibit an accelerated hematocrit response to both acute (PHZ treatment) and chronic (EPO administration) erythroid stimulation which lasts longer than in wild-type (J:78540)
• at 15-20 months of age (J:78348)
• mutants become anemic from 15 months of age (J:78348)
• erythrocytes with Howell-Jolly bodies are seen in the blood (J:78348)
• tear-drop poikilocytes are seen in the blood (J:78348)
• erythrocytes with polychromatophilia are seen in the blood (J:78348)
• 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)
• overall erythroid precursor cell content in the marrow is lower than in wild-type (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)
• progressive increase in the percentages of neutrophils by 15-20 months of age (J:78348)
• progressive decrease in the percentage of lymphocytes (J:78348)
• transition of the major hematopoietic site from the marrow to the spleen (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)
• number of megakaryocyte progenitor cells (CFU-Mk) circulating in the blood increases by 18-20 months of age (J:78348)
• 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 (J:78348)
• however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age (J:78348)
(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)
(J:78348)
• platelets appear abnormal and bigger than normal platelets (J:78540)
• accumulation of reticulin fibers with age in the spleen (J:78348)
• 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 (J:78348)
• however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age (J:78348)
• the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes (J:78540)
• red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells (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)
• spleen contains 3 times more cells than wild-type (J:78540)

homeostasis/metabolism
• mutants recover 2 days faster from the PHZ-induced anemia than controls (J:78540)

immune system
• progressive increase in the percentages of neutrophils by 15-20 months of age (J:78348)
• progressive decrease in the percentage of lymphocytes (J:78348)
• accumulation of reticulin fibers with age in the spleen (J:78348)
• 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 (J:78348)
• however, due to the overall decrease in spleen cellularity, the total number of progenitor cells of all types in the spleen decreases with age (J:78348)
• the interfollicular space of the red pulp is filled with abnormally large and dysplastic megakaryocytes (J:78540)
• red pulp and subcapsulary space are filled with lymphocyte-sized cells resembling immature erythroid cells (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)
• spleen contains 3 times more cells than wild-type (J:78540)

skeleton
• 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)
• myelofibrotic degeneration of the marrow and spleen with age; about 7 times more megakaryocytes in the bone marrow than controls (J:78348)
• expression of growth factor genes implicated in the development of myelofibrosis is increased in the marrow (J:78348)
• 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 (J:78348)
• starting at 12 months of age, an increase of bone trabeculae is seen in the bone marrow (J:78348)
• in the oldest mice, increased osteogenesis eventually occludes the femoral cavity (J:78348)

liver/biliary system
• 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 (J:78348)

mortality/aging
• 9 of 178 mutants born alive die within the first 15 days of life (J:78348)
• most mutants die between 14 and 20 months of age, and only 9 survive past 20 months of age (J:78348)
• only 30% of pregnancies induced result in viable pups (J:78348)

Mouse Models of Human Disease
OMIM IDRef(s)
Myelofibrosis 254450 J:78348