Phenotypes Associated with This Genotype

Genotype
MGI:5582314

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

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

mortality/aging

premature death ( J:87429 )

• mice survive for a median of 84 days after pIpC injection

hematopoietic system

increased splenocyte proliferation ( J:87429 )

• increase in the number of proliferating splenocytes in pIpC treated mice; most of these proliferating cells are Mac1+/Gr1 lo or Ter119+

enlarged spleen ( J:87429 , J:115071 )

• spleens of pIpC-treated moribund mice are massively enlarged (J:87429)

• in pIpC treated mice (J:115071)

abnormal erythropoiesis ( J:87429 , J:115071 )

• mice treated with pIpC show large numbers of proliferating splenic Ter199+ cells, indicating that erythropoiesis is ineffective (J:87429)

• the erythroid progenitor compartment is massively expanded in the spleen of pIpC treated mice (J:115071)

• pIpC treated mice show normal numbers of early erythroid cells in the bone marrow but a paucity of all the more mature TER119 hi populations, indicating an inefficient transition from TER119- to TER119 hi stages of erythropoiesis (J:115071)

• bone marrow from pIpC treated mice forms abnormally large BFU-E colonies characterized by both erythropoietin-independent growth and hypersensitivity to erythropoietin (J:115071)

• spleen of pIpC treated mice contains increase of immature CD71 hi TER119-/lo cells and large numbers of TER119 hi erythroblasts (J:115071)

abnormal myelopoiesis ( J:87429 )

• pIpC injected mice develop a myeloproliferative disease with excess monocytes

• bone marrow mononuclear cells from pIpC treated mice form significant numbers of colony-forming unit granulocyte-macrophage (CFU-GM) colonies in the absence of exogenous cytokines while wild-type cells do not

• CFU-GM shows an increased proliferative response without added cytokines (9-fold) or to GM-CSF (19-fold increase) or IL-3 (37-fold increase)

myeloid hyperplasia ( J:87429 )

• mice show abundant myeloid cells at various stages of differentiation after pIpC injection

anemia ( J:87429 , J:115071 )

• pups injected with pIpC develop anemia (J:87429)

• however, normal platelet counts are seen in pIpC injected mice (J:87429)

decreased mean corpuscular hemoglobin ( J:115071 )

• in pIpC treated mice

anisopoikilocytosis ( J:115071 )

• in pIpC treated mice

polychromatophilia ( J:115071 )

• in pIpC treated mice

increased leukocyte cell number ( J:87429 )

• pups injected with pIpC at 21 days of age develop progressive leukocytosis that is evident 3 weeks after pIpC injection

increased monocyte cell number ( J:87429 )

• mice show an expanded population of Mac-1+, Gr-1 lo cells, indicating an expansion of immature monocytic cells

reticulocytosis ( J:115071 )

• in pIpC treated mice

immune system

increased splenocyte proliferation ( J:87429 )

• increase in the number of proliferating splenocytes in pIpC treated mice; most of these proliferating cells are Mac1+/Gr1 lo or Ter119+

enlarged spleen ( J:87429 , J:115071 )

• spleens of pIpC-treated moribund mice are massively enlarged (J:87429)

• in pIpC treated mice (J:115071)

abnormal myelopoiesis ( J:87429 )

• pIpC injected mice develop a myeloproliferative disease with excess monocytes

• bone marrow mononuclear cells from pIpC treated mice form significant numbers of colony-forming unit granulocyte-macrophage (CFU-GM) colonies in the absence of exogenous cytokines while wild-type cells do not

• CFU-GM shows an increased proliferative response without added cytokines (9-fold) or to GM-CSF (19-fold increase) or IL-3 (37-fold increase)

myeloid hyperplasia ( J:87429 )

• mice show abundant myeloid cells at various stages of differentiation after pIpC injection

increased leukocyte cell number ( J:87429 )

• pups injected with pIpC at 21 days of age develop progressive leukocytosis that is evident 3 weeks after pIpC injection

increased monocyte cell number ( J:87429 )

• mice show an expanded population of Mac-1+, Gr-1 lo cells, indicating an expansion of immature monocytic cells

liver/biliary system

enlarged liver ( J:87429 )

• pIpC injected mice show moderate hepatomegaly with myeloid infiltration, particularly in periportal areas

cellular

increased splenocyte proliferation ( J:87429 )

• increase in the number of proliferating splenocytes in pIpC treated mice; most of these proliferating cells are Mac1+/Gr1 lo or Ter119+

homeostasis/metabolism

increased circulating erythropoietin level ( J:115071 )

• serum erythropoietin levels are increased in proportion to anemia in pIpC treated mice

growth/size/body

enlarged liver ( J:87429 )

• pIpC injected mice show moderate hepatomegaly with myeloid infiltration, particularly in periportal areas

enlarged spleen ( J:87429 , J:115071 )

• spleens of pIpC-treated moribund mice are massively enlarged (J:87429)

• in pIpC treated mice (J:115071)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	acute myeloid leukemia	DOID:9119	OMIM:601626	J:87429
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:87429 , J:115071