Phenotypes associated with this allele

• Allele Symbol: Npm1⁺
• Allele Name: wild type
• Allele ID: MGI:2433597
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Npm1^Gt(OST331547)Lex/Npm1^+	B6;129S5-Npm1^Gt(OST331547)Lex/Mmucd	MGI:5442748
ht2	Npm1^tm1Hft/Npm1^+	involves: 129	MGI:5478730
ht3	Npm1^tm1Ppp/Npm1^+	involves: 129S1/Sv * C57BL/6	MGI:3606861
cn4	Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+ Npm1^tm1Trow/Npm1^+	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Npm1^tm1Trow	MGI:6286134
cn5	Dnmt3a^tm1Trow/Dnmt3a^+ Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj/Gt(ROSA)26Sor^+ Npm1^tm1Trow/Npm1^+ Tg(Mx1-cre)1Cgn/0	B6.Cg-Gt(ROSA)26Sor^tm3(CAG-flpo/ERT2)Alj Npm1^tm1Trow Dnmt3a^tm1Trow Tg(Mx1-cre)1Cgn	MGI:6286136
cn6	Gt(ROSA)26Sor^tm4(CAG-hsb5)Nki/Gt(ROSA)26Sor^+ Npm1^tm1Gsva/Npm1^+ TgTn(pb-sb-GrOnc)#aGsva/0 Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:5007701
cn7	Npm1^tm1Gsva/Npm1^+ Tg(Mx1-cre)1Cgn/0	involves: C57BL/6 * CBA	MGI:5004900
cx8	Npm1^tm1Ppp/Npm1^+ Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3606864
cx9	Npm1^tm1Ppp/Npm1^+ Tg(IghMyc)22Bri/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:3606872

Genotype
MGI:5442748

ht1

• Allelic Composition: Npm1^{Gt(OST331547)Lex}/Npm1⁺
• Genetic Background: B6;129S5-Npm1^{Gt(OST331547)Lex}/Mmucd

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

hematopoietic system

hematopoietic system phenotype ( J:188985 )

N • unlike Npm1^tm1Ppp heterozygotes, mice exhibit normal blood counts

N • the total number and frequency of methylcellulose colony-forming unit (CFU)-granulocyte/monocyte and CFU-granulocyte/erythrocyte/monocyte/megakaryocyte is normal

increased hematopoietic stem cell number ( J:188985 )

• 1.4-fold

abnormal hematopoietic stem cell physiology ( J:188985 )

• hematopoietic stem cells exhibit reduced engraftment potential compared with control cells

Genotype
MGI:5478730

ht2

• Allelic Composition: Npm1^tm1Hft/Npm1⁺
• Genetic Background: involves: 129

Splenomegaly and follicle structure changes in Npm1^tm1Hft/Npm1⁺ mice

hematopoietic system

hematopoietic system phenotype ( J:194999 )

N • mice exhibit normal red cell volumes, red blood cell count, hemoglobin and mean platelet volume

abnormal granulocyte differentiation ( J:194999 )

• mice without MPD exhibit increased granulocyte-macrophage progenitors compared with wild-type mice

enlarged spleen ( J:194999 )

• in mice with myeloproliferative disease

increased spleen weight ( J:194999 )

• in mice with myeloproliferative disease

myeloid hyperplasia ( J:194999 )

• some mice exhibit myeloproliferative disease (MPD) features

• mice without MPD exhibit still myeloid expansion

extramedullary hematopoiesis ( J:194999 )

• in mice with myeloproliferative disease with megakaryocyte infiltration

abnormal bone marrow cell morphology/development ( J:194999 )

• the bone marrow of mice without MPD exhibits expansion of myeloid compartment with an increase in HSPC and progenitor cells compared with wild-type mice

• mice with or without MPD exhibit age-dependent compromised cobblestone area formation compared with wild-type cells

abnormal common myeloid progenitor cell morphology ( J:194999 )

• increased colony forming units from the bone marrow of mice with MPD

• increased progenitor cells in the bone marrow of mice without MPD

thrombocytosis ( J:194999 )

• in some mice late in life

increased leukocyte cell number ( J:194999 )

• in some mice at various stages

increased granulocyte number ( J:194999 )

• mature granulocytes in in the blood and bone marrow of mice with myeloproliferative disease

increased monocyte cell number ( J:194999 )

• in the peripheral blood of mice without MPD after age 17 to 18 months

increased hematopoietic stem cell number ( J:194999 )

• in the bone marrow of mice without MPD

abnormal spleen B cell follicle morphology ( J:194999 )

• mice with myeloproliferative disease exhibit effacement of follicle structure in the spleen

immune system

abnormal granulocyte differentiation ( J:194999 )

• mice without MPD exhibit increased granulocyte-macrophage progenitors compared with wild-type mice

enlarged spleen ( J:194999 )

• in mice with myeloproliferative disease

increased spleen weight ( J:194999 )

• in mice with myeloproliferative disease

myeloid hyperplasia ( J:194999 )

• some mice exhibit myeloproliferative disease (MPD) features

• mice without MPD exhibit still myeloid expansion

increased leukocyte cell number ( J:194999 )

• in some mice at various stages

increased granulocyte number ( J:194999 )

• mature granulocytes in in the blood and bone marrow of mice with myeloproliferative disease

increased monocyte cell number ( J:194999 )

• in the peripheral blood of mice without MPD after age 17 to 18 months

abnormal spleen B cell follicle morphology ( J:194999 )

• mice with myeloproliferative disease exhibit effacement of follicle structure in the spleen

cellular

abnormal granulocyte differentiation ( J:194999 )

• mice without MPD exhibit increased granulocyte-macrophage progenitors compared with wild-type mice

neoplasm

neoplasm ( J:194999 )

N • mice do not develop acute myeloid leukemia

growth/size/body

enlarged spleen ( J:194999 )

• in mice with myeloproliferative disease

increased spleen weight ( J:194999 )

• in mice with myeloproliferative disease

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	acute myeloid leukemia	DOID:9119	OMIM:601626	J:194999

Genotype
MGI:3606861

ht3

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

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

Genotype
MGI:6286134

cn4

• Allelic Composition: Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺; Npm1^tm1Trow/Npm1⁺
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Npm1^tm1Trow

hematopoietic system

abnormal bone marrow hematopoietic cell morphology ( J:272803 )

♀ • increase in total number of colony forming units are found in whole bone marrow cells 4 months post-tamoxifen injection

increased granulocyte monocyte progenitor cell number ( J:272803 )

♀ • expansion of granulocyte and granulocyte-macrophage colony types are found in whole bone marrow cells 4 months post-tamoxifen injection

decreased hematopoietic stem cell number ( J:272803 )

♀ • decrease in frequency and total number of long term hematopoietic stem cells 4 months post-tamoxifen injection

♀ • decrease in total number of short term hematopoietic stem cells 4 months post-tamoxifen injection

abnormal bone marrow cell physiology ( J:272803 )

♀ • bone marrow cells transplanted into lethally irradiated recipients and treated with pIpC and tamoxifen results in death in a 29% of animals in a 440 day period due to myeloproliferative disorder

Genotype
MGI:6286136

cn5

• Allelic Composition: Dnmt3a^tm1Trow/Dnmt3a⁺; Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj}/Gt(ROSA)26Sor⁺; Npm1^tm1Trow/Npm1⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm3(CAG-flpo/ERT2)Alj} Npm1^tm1Trow Dnmt3a^tm1Trow Tg(Mx1-cre)1Cgn

hematopoietic system

abnormal bone marrow cell physiology ( J:272803 )

♀ • bone marrow cells transplanted into lethally irradiated recipients and treated with pIpC and tamoxifen results in death in a 100% of animals in a 440 day period

♀ • in 33% of mice death is the result of myeloproliferative disorder (MPD)

♀ • in 67% of mice death is the result of mixed myelodysplastic syndrome and myeloproliferative disorder (MDS/MPD)

♀ • bone marrow cells from MDS/MPD or MPD primary transplants transplanted into sublethally irradiated secondary recipients results in 100% lethality due to acute myeloid leukemia (AML)

Genotype
MGI:5007701

cn6

• Allelic Composition: Gt(ROSA)26Sor^{tm4(CAG-hsb5)Nki}/Gt(ROSA)26Sor⁺; Npm1^tm1Gsva/Npm1⁺; TgTn(pb-sb-GrOnc)#aGsva/0; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

premature death ( J:172071 )

• mean survival of pIpC-treated mice is 99 days compared with 150 days for Gt(Rosa)26Sor^{tm4(CAG-hsb5)Nki} Gt(Rosa)26Sor⁺ Tg(Mx1-cre)1Cgn TgTn(pb-sb-GrOnc)#aGsva control mice

neoplasm

increased leukemia incidence ( J:172071 )

• all mice develop aggressive leukemia and/or lymphoma within a year of pIpC induction

increased acute promyelocytic leukemia incidence ( J:172071 )

• in pIpC-treated mice

increased lymphoma incidence ( J:172071 )

• all mice develop aggressive leukemia and/or lymphoma within a year of pIpC induction

• however, pIpC-treated mice do not develop T cell lymphomas unlike in control mice

increased B cell derived lymphoma incidence ( J:172071 )

• in some pIpC-treated mice

increased hemangiosarcoma incidence ( J:172071 )

• angiosarcoma in some pIpC-treated mice

Genotype
MGI:5004900

cn7

• Allelic Composition: Npm1^tm1Gsva/Npm1⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:172071 )

• due to acute myeloid leukemia, survival of pIpC-treated mice is 617 days compared with 769 days for wild-type mice

hematopoietic system

enlarged spleen ( J:172071 )

• in pIpC-treated mice

increased spleen weight ( J:172071 )

• in pIpC-treated mice

abnormal common myeloid progenitor cell morphology ( J:172071 )

• with serial replating, cells from pIpC-treated mice exhibit increased myeloid progenitor colony formation on methylcellulose compared with cells from wild-type mice

increased mean corpuscular volume ( J:172071 )

• in pIpC-treated mice

increased mean platelet volume ( J:172071 )

• in pIpC-treated mice

decreased B cell number ( J:172071 )

• pIpC-treated mice exhibit a decrease in late B cells (B220+ CD19+) compared with wild-type mice

increased leukocyte cell number ( J:172071 )

• in pIpC-treated mice

increased granulocyte number ( J:172071 )

• in pIpC-treated mice

neoplasm

increased acute promyelocytic leukemia incidence ( J:172071 )

• acute myeloid leukemia with maturation in pIpC-treated mice

increased B cell derived lymphoma incidence ( J:172071 )

• in 6 of 13 pIpC-treated mice

liver/biliary system

enlarged liver ( J:172071 )

• in pIpC-treated mice

increased liver weight ( J:172071 )

• in pIpC-treated mice

immune system

enlarged spleen ( J:172071 )

• in pIpC-treated mice

increased spleen weight ( J:172071 )

• in pIpC-treated mice

decreased B cell number ( J:172071 )

• pIpC-treated mice exhibit a decrease in late B cells (B220+ CD19+) compared with wild-type mice

increased leukocyte cell number ( J:172071 )

• in pIpC-treated mice

increased granulocyte number ( J:172071 )

• in pIpC-treated mice

growth/size/body

enlarged liver ( J:172071 )

• in pIpC-treated mice

increased liver weight ( J:172071 )

• in pIpC-treated mice

enlarged spleen ( J:172071 )

• in pIpC-treated mice

increased spleen weight ( J:172071 )

• in pIpC-treated mice

Genotype
MGI:3606864

cx8

• Allelic Composition: Npm1^tm1Ppp/Npm1⁺; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6

cellular

increased fibroblast proliferation ( J:101494 )

• MEFs are fully rescued in the growth defect at early passage (P3-P5) that is seen in heterozygous Npm1^tm1Ppp mice and grow faster than wildtype controls

Genotype
MGI:3606872

cx9

• Allelic Composition: Npm1^tm1Ppp/Npm1⁺; Tg(IghMyc)22Bri/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * SJL

neoplasm

abnormal tumor morphology ( J:101494 )

• all lymphomas have numerical chromosomal abnormalities unlike in Tg(IghMyc)22Bri animals, however only 1 of 4 tumors show structural abnormalities that are seen in the transgenic mice alone

increased B cell derived lymphoma incidence ( J:101494 )

• B cell lymphoma onset is significantly accelerated compared to Tg(IghMyc)22Bri mice

• all lymphomas have numerical chromosomal abnormalities unlike Tg(IghMyc)22Bri animals, however only 1 of 4 tumors show structural abnormalities that are seen in the transgenic mice alone