Phenotypes associated with this allele

• Allele Symbol: Npm1^tm1Ppp
• Allele Name: targeted mutation 1, Pier Paolo Pandolfi
• Allele ID: MGI:3604807
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Npm1^tm1Ppp/Npm1^tm1Ppp	involves: 129S1/Sv * C57BL/6	MGI:3606858
ht2	Npm1^tm1Ppp/Npm1^+	involves: 129S1/Sv * C57BL/6	MGI:3606861
cx3	Npm1^tm1Ppp/Npm1^tm1Ppp Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3606865
cx4	Npm1^tm1Ppp/Npm1^+ Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3606864
cx5	Npm1^tm1Ppp/Npm1^tm1Ppp Trp53^tm1Brd/Trp53^+	involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3606866
cx6	Npm1^tm1Ppp/Npm1^+ Tg(IghMyc)22Bri/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:3606872

Genotype
MGI:3606858

hm1

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

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:101494 )

• die between E11.5 and E12.5

hematopoietic system

abnormal embryonic hematopoiesis ( J:101494 )

• decrease in the number of embryonic erythroblasts at the interface of maternal and fetal blood

• great reduction in the number of hematopoietic precursors in the blood islands of yolk sacs

• 30-40% of blood cell precursors isolated from yolk sacs contain large multinucleated cells with up to four nuclei and numerous centrosomes

anemia ( J:101494 )

embryo

absent vitelline blood vessels ( J:101494 )

• yolk sac appears devoid of blood supply

increased embryonic tissue cell apoptosis ( J:101494 )

• increased apoptosis in embryos, especially in neural tissue, however no difference in the number of proliferating cells

decreased embryo size ( J:101494 )

• embryos are consistently smaller in size

small placenta ( J:101494 )

• placental structures are smaller but normally developed

abnormal visceral yolk sac blood island morphology ( J:101494 )

• number of blood islands is reduced

abnormal embryonic hematopoiesis ( J:101494 )

• decrease in the number of embryonic erythroblasts at the interface of maternal and fetal blood

• great reduction in the number of hematopoietic precursors in the blood islands of yolk sacs

• 30-40% of blood cell precursors isolated from yolk sacs contain large multinucleated cells with up to four nuclei and numerous centrosomes

growth/size/body

decreased embryo size ( J:101494 )

• embryos are consistently smaller in size

cellular

abnormal cell cycle ( J:101494 )

• MEFs undergo premature senescence and growth arrest with an accumulation of cells with a 4N DNA content and polyploidy, consistent with a tetraploid arrest in G1 phase

• up to 30% of interphase MEFs contain multiple centrosomes (3 or more) and multi-polar spindles

increased embryonic tissue cell apoptosis ( J:101494 )

• increased apoptosis in embryos, especially in neural tissue, however no difference in the number of proliferating cells

decreased fibroblast proliferation ( J:101494 )

• early passage MEFs (P2-P6) have decreased cell proliferation rates

liver/biliary system

absent liver ( J:101494 )

• E12.5 embryos lack a fetal liver structure

nervous system

abnormal brain morphology ( J:101494 )

• subdivision between metencephalon and mesencephalon is shifted anteriorly

absent forebrain ( J:101494 )

• absent forebrain at E10.5

vision/eye

anophthalmia ( J:101494 )

cardiovascular system

absent vitelline blood vessels ( J:101494 )

• yolk sac appears devoid of blood supply

integument

pallor ( J:101494 )

• embryos are pale as early as E9.5

Genotype
MGI:3606861

ht2

• 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:3606865

cx3

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

mortality/aging

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

• embryonic lethality by E16.5

Genotype
MGI:3606864

cx4

• 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:3606866

cx5

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

mortality/aging

embryonic lethality, complete penetrance ( J:101494 )

• embryonic lethality by E13.5

Genotype
MGI:3606872

cx6

• 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