Phenotypes Associated with This Genotype

Genotype
MGI:3035835

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

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

mortality/aging

premature death ( J:88163 )

• survival for around 35 days after pI-pC treatment

• survival of around 58 days even without pI-pC treatment

neoplasm

increased lymphoblastic lymphoma incidence ( J:88163 )

• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas

• 2 of 6 non pIpC treated mice show thymic lymphomas

increased lung adenoma incidence ( J:88163 )

• 10 of 17 mice injected with pIpC exhibit multiple nodules in the lungs consisting of proliferating type II penumocytes

• 5 of 6 non pIpC treated mice show pulmonary adenomas

increased papilloma incidence ( J:88163 )

• squamous papillomas

increased oral papilloma incidence ( J:88163 )

• 8 of 25 mice injected with pIpC develop squamous papillomas involving the oral mucosa

• 2 of 6 non-pIpC treated mice show oral squamous papillomas

increased esophageal papilloma incidence ( J:88163 )

• 8 of 22 mice injected with pIpC develop squamous papillomas involving the esophageal mucosa

increased skin papilloma incidence ( J:88163 )

• 12 of 19 mice injected with pIpC develop squamous papillomas involving the anal and vulvo-vaginal skin and 8 of 22 mice develop squamous papillomas involving the ear

• 2 of 6 non-pIpC treated mice show ear squamous papillomas

growth/size/body

increased oral papilloma incidence ( J:88163 )

• 8 of 25 mice injected with pIpC develop squamous papillomas involving the oral mucosa

• 2 of 6 non-pIpC treated mice show oral squamous papillomas

cachexia ( J:88163 )

• becoming emaciated

enlarged spleen ( J:88163 )

• mice injected with pIpC develop moderate to severe splenomegaly

hematopoietic system

increased lymphoblastic lymphoma incidence ( J:88163 )

• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas

• 2 of 6 non pIpC treated mice show thymic lymphomas

enlarged spleen ( J:88163 )

• mice injected with pIpC develop moderate to severe splenomegaly

abnormal definitive hematopoiesis ( J:88163 )

• develop lethal hematopoietic disease

abnormal myelopoiesis ( J:88163 )

• 4-7 week old mice injected with pIpC develop a myeloproliferative disorder

• bone marrow of mice injected with pIpC shows myelomonocytic expansion

• all mice that are not treated with pIpC also develop a hematopoietic disease, however these mice exhibit expression of the mutant Kras, indicating that most likely endogenous IFN expression is sufficient to induce the cre transgene

• bone marrow cells from pIpC injected mice readily form colonies, predominately monocyte colony-forming units (M-CFUs) in a growth factor-independent manner unlike controls

myeloid hyperplasia ( J:88163 )

• myeloproliferative phenotype

• myeloid hyperplasia of bone marrow

extramedullary hematopoiesis ( J:88163 )

• expansion of red pulp in spleen by granulocyte/monocyte lineages in 11 out of 16 cases

• erythroid expansion was seen in red pulp of spleen in 5 of 16 cases

• the liver shows perivascular and periportal infiltration by myeloid and erythroid cell populations

anemia ( J:88163 )

• mice injected with pIpC become anemic

abnormal erythrocyte morphology ( J:88163 )

decreased hematocrit ( J:88163 )

• mice injected with pIpC have a mean hematocrit of 27% compared with 45% in controls

increased leukocyte cell number ( J:88163 )

• leukocytosis, usually involving increases in granulocytes, in both pIpC and non-pIpC treated mice

increased granulocyte number ( J:88163 )

• leukocytosis in mice injected with pIpC is mainly due to an increase in granulocyte population

increased spleen red pulp amount ( J:88163 )

• mice injected with pIpC show expansion of the red pulp by varying degrees of granulocytic

immune system

increased lymphoblastic lymphoma incidence ( J:88163 )

• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas

• 2 of 6 non pIpC treated mice show thymic lymphomas

enlarged spleen ( J:88163 )

• mice injected with pIpC develop moderate to severe splenomegaly

abnormal myelopoiesis ( J:88163 )

• 4-7 week old mice injected with pIpC develop a myeloproliferative disorder

• bone marrow of mice injected with pIpC shows myelomonocytic expansion

• all mice that are not treated with pIpC also develop a hematopoietic disease, however these mice exhibit expression of the mutant Kras, indicating that most likely endogenous IFN expression is sufficient to induce the cre transgene

• bone marrow cells from pIpC injected mice readily form colonies, predominately monocyte colony-forming units (M-CFUs) in a growth factor-independent manner unlike controls

myeloid hyperplasia ( J:88163 )

• myeloproliferative phenotype

• myeloid hyperplasia of bone marrow

increased leukocyte cell number ( J:88163 )

• leukocytosis, usually involving increases in granulocytes, in both pIpC and non-pIpC treated mice

increased granulocyte number ( J:88163 )

• leukocytosis in mice injected with pIpC is mainly due to an increase in granulocyte population

increased spleen red pulp amount ( J:88163 )

• mice injected with pIpC show expansion of the red pulp by varying degrees of granulocytic

lymphoid hyperplasia ( J:88163 )

• 6 of 17 mice injected with pIpC develop nodal lymphoid hyperplasia

liver/biliary system

abnormal hepatobiliary system morphology ( J:88163 )

• perivascular and periportal infiltration in liver by myeloid and erythroid cells similar to what is seen in spleen

integument

ruffled hair ( J:88163 )

• ruffled fur

increased skin papilloma incidence ( J:88163 )

• 12 of 19 mice injected with pIpC develop squamous papillomas involving the anal and vulvo-vaginal skin and 8 of 22 mice develop squamous papillomas involving the ear

• 2 of 6 non-pIpC treated mice show ear squamous papillomas

digestive/alimentary system

increased esophageal papilloma incidence ( J:88163 )

• 8 of 22 mice injected with pIpC develop squamous papillomas involving the esophageal mucosa

endocrine/exocrine glands

increased lymphoblastic lymphoma incidence ( J:88163 )

• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas

• 2 of 6 non pIpC treated mice show thymic lymphomas

respiratory system

increased lung adenoma incidence ( J:88163 )

• 10 of 17 mice injected with pIpC exhibit multiple nodules in the lungs consisting of proliferating type II penumocytes

• 5 of 6 non pIpC treated mice show pulmonary adenomas

craniofacial

increased oral papilloma incidence ( J:88163 )

• 8 of 25 mice injected with pIpC develop squamous papillomas involving the oral mucosa

• 2 of 6 non-pIpC treated mice show oral squamous papillomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:88163