Phenotypes Associated with This Genotype

Genotype
MGI:3606861

• Allelic Composition: Npm1^tm1Ppp/Npm1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:101494 )

• ratio between wildtype and heterozygous mice is about 1:1.5, however no neonatal lethality is observed, indicating that some embryos die in utero, even though none were found dead before E14.5

immune system

abnormal thrombopoiesis ( J:101494 )

• a few heterozygotes exhibit an increase in thrombocyte numbers and in general, the platelet counts show a wider scatter than in wildtype

hematopoietic system

abnormal thrombopoiesis ( J:101494 )

• a few heterozygotes exhibit an increase in thrombocyte numbers and in general, the platelet counts show a wider scatter than in wildtype

increased bone marrow cell number ( J:101494 )

• bone marrow shows hypercellularity of red blood cell precursors and an increase in the relative ratio of erythroblast/myeloid precursors

abnormal megakaryocyte morphology ( J:101494 )

• subset of heterozygotes exhibit megakaryocyte dyspoiesis, including cells with multiple separated nuclei, cells with small oval nuclei in mature cytoplasm, or cells with hypolobated nuclei

• a few heterozygotes show an increase in megakaryocyte numbers

abnormal proerythroblast morphology ( J:101494 )

• high proportion of dysplastic erythroid precursors, which include binucleated cells, cells with abnormal mitosis and cells with nuclear fragmentation and irregular nuclear contours in the bone marrow

• bone marrow shows an increase in the percentage of immature erythroblasts and a decrease in cells in the advanced stages of erythroid differentiation

increased mean corpuscular volume ( J:101494 )

• seen in about 80% of 6-18 month old heterozygotes

anisocytosis ( J:101494 )

• increase in red cell distribution width indicating an overall increase in size of erythrocytes, however did not observe reticulocytosis or differences in red blood cell counts or hemoglobin levels

reticulocytopenia ( J:101494 )

• a few heterozygotes exhibit very low reticulocyte counts

cellular

abnormal cell proliferation ( J:101494 )

• early passage MEFs (P2-P6) have decreased cell proliferation rates, however later passage cells (P5-P8) have higher proliferation rates and show an immortal phenotype

chromosome breakage ( J:101494 )

• MEFs contain supernumery centrosomes

• later passage MEFs exhibit high levels of anueploidy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:101494