Phenotypes Associated with This Genotype

Genotype
MGI:5575662

• Allelic Composition: Asxl1^tm1.1Iaai/Asxl1^tm1.1Iaai; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

hematopoietic system

abnormal definitive hematopoiesis ( J:208092 )

• increase in the absolute number of immunophenotypically defined hematopoietic stem cells at 6 weeks of age, however a decrease in serial plating in vitro is seen, indicating a defect in self-renewal of hematopoietic stem cells

• transplantation experiments show that hematopoietic stem cells show impaired self-renewal

• transplantation of whole bone marrow from mutants into lethally irradiated recipients results in a lethal hematopoietic disorder

abnormal myelopoiesis ( J:208092 )

• 6 month old mice show dysplasia of circulating myeloid cells

• analysis of sorted myeloid progenitor cells from 6 week old mice shows a decrease in colony output of sorted common myeloid progenitors, granulocyte/macrophage progenitors, and megakaryocyte/erythroid progenitors

anemia ( J:208092 )

• develop progressive anemia that is most apparent at 6-12 months of age

decreased bone marrow cell number ( J:208092 )

• mice develop progressive bone marrow hypocellularity beginning at 6 weeks of age that is still seen at 24 weeks of age

increased erythroid progenitor cell number ( J:208092 )

• 1.4- to 2-fold increase in CD71+/Ter119- erythoroid precursor cells in the bone marrow and spleen, indicating impaired erythroid differentiation

decreased hemoglobin content ( J:208092 )

• hemoglobin is reduced at between 6 and 12 months of age, but not in mice younger than 6 months

increased nucleated erythrocyte cell number ( J:208092 )

• 6 month old mice show frequent circulating nucleated red cells

decreased leukocyte cell number ( J:208092 )

• develop progressive leukopenia that is most apparent at 6-12 months of age

• leukopenia is predominately as a result of decreased B220+ mature B cells, CD11b+Gr1+ neutrophils, and CD11b+Gr1- monocytes

decreased neutrophil cell number ( J:208092 )

• decrease in CD11b+Gr1+ neutrophils

decreased mature B cell number ( J:208092 )

• decrease in B220+ mature B cells

decreased monocyte cell number ( J:208092 )

• decrease in CD11b+Gr1- monocytes

abnormal hematopoietic stem cell morphology ( J:208092 )

• mice show increased apoptosis and altered cell cycle distribution (decrease in S-phase) of hematopoietic stem cells

increased hematopoietic stem cell number ( J:208092 )

• mice show an increase in the frequency and total number of hematopoietic stem cells

decreased splenocyte number ( J:208092 )

• mice develop progressive splenic hypocellularity beginning at 6 weeks of age that is still seen at 24 weeks of age

immune system

abnormal myelopoiesis ( J:208092 )

• 6 month old mice show dysplasia of circulating myeloid cells

• analysis of sorted myeloid progenitor cells from 6 week old mice shows a decrease in colony output of sorted common myeloid progenitors, granulocyte/macrophage progenitors, and megakaryocyte/erythroid progenitors

decreased leukocyte cell number ( J:208092 )

• develop progressive leukopenia that is most apparent at 6-12 months of age

• leukopenia is predominately as a result of decreased B220+ mature B cells, CD11b+Gr1+ neutrophils, and CD11b+Gr1- monocytes

decreased neutrophil cell number ( J:208092 )

• decrease in CD11b+Gr1+ neutrophils

decreased mature B cell number ( J:208092 )

• decrease in B220+ mature B cells

decreased monocyte cell number ( J:208092 )

• decrease in CD11b+Gr1- monocytes

decreased splenocyte number ( J:208092 )

• mice develop progressive splenic hypocellularity beginning at 6 weeks of age that is still seen at 24 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:208092