Phenotypes Associated with This Genotype

Genotype
MGI:5544056

• Allelic Composition: Nf1^tm1Par/Nf1^tm1Par; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

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

mortality/aging

premature death ( J:90973 )

• 50% of pIpC treated mice die by 7.5 months of age

hematopoietic system

abnormal definitive hematopoiesis ( J:90973 )

• pIpC injected mice at 3 to 5 days of age develop overt signs of myeloproliferative disease beginning between 5 and 6 months of age

• pIpC injected mice show a shift in hematopoiesis from the marrow to the spleen

abnormal common myeloid progenitor cell morphology ( J:90973 )

• myeloid progenitors from pIpC injected mice show increased proliferation

abnormal myelopoiesis ( J:90973 )

• spleen from pIpC injected mice shows a massive increase in myelopoiesis

abnormal bone marrow cell morphology/development ( J:90973 )

• apoptosis is reduced in the bone marrow of pIpC injected mice

• bone marrow from pIpC injected mice is highly cellular, comprised of myeloid cells at various stages of differentiation

• increase in numbers of immature monocytic cells in the bone marrow of pIpC treated mice

• bone marrow from pIpC injected mice contains elevated numbers of CFU-GM and an increase in the numbers of CFU-GM that are hypersensitive to granulocyte-macrophage colony stimulating factor (GM-CSF) and CFU-GM colonies are larger than normal and show abnormal spreading morphology

abnormal hematopoietic cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated numbers of differentiated lymphoid cells by 3 months of age

increased leukocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated leukocyte counts by 3 months of age

• cultures from pIpC injected mice show an increase in the percentage of monocyte-macrophage cells

increased granulocyte number ( J:90973 )

• pIpC injected mice show an increase in numbers of differentiated granulocytic cells

increased neutrophil cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal neutrophils by 3 months of age

increased lymphocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal lymphocytes by 3 months of age

increased monocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal monocytes by 3 months of age

• pIpC injected mice show an increase in numbers of immature monocytic cells in the bone marrow

abnormal myeloid leukocyte morphology ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated numbers of differentiated myeloid cells by 3 months of age

abnormal spleen morphology ( J:90973 )

• spleens from pIpC injected mice contain large numbers of CFU-GM

enlarged spleen ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit progressive splenomegaly with extensive infiltration of myeloid cells at various stages of maturation

behavior/neurological

hunched posture ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit abnormal gait by 5-6 months of age

abnormal gait ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit hunching by 5-6 months of age

immune system

abnormal myelopoiesis ( J:90973 )

• spleen from pIpC injected mice shows a massive increase in myelopoiesis

increased leukocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated leukocyte counts by 3 months of age

• cultures from pIpC injected mice show an increase in the percentage of monocyte-macrophage cells

increased lymphocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal lymphocytes by 3 months of age

abnormal myeloid leukocyte morphology ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit elevated numbers of differentiated myeloid cells by 3 months of age

increased granulocyte number ( J:90973 )

• pIpC injected mice show an increase in numbers of differentiated granulocytic cells

increased neutrophil cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal neutrophils by 3 months of age

increased monocyte cell number ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit increased numbers of morphologically normal monocytes by 3 months of age

• pIpC injected mice show an increase in numbers of immature monocytic cells in the bone marrow

abnormal spleen morphology ( J:90973 )

• spleens from pIpC injected mice contain large numbers of CFU-GM

enlarged spleen ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit progressive splenomegaly with extensive infiltration of myeloid cells at various stages of maturation

integument

disheveled coat ( J:90973 )

• pIpC injected mice at 3 to 5 days of age have a disheveled appearance by 5-6 months of age

growth/size/body

enlarged spleen ( J:90973 )

• pIpC injected mice at 3 to 5 days of age exhibit progressive splenomegaly with extensive infiltration of myeloid cells at various stages of maturation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile myelomonocytic leukemia		DOID:0050458	OMIM:607785	J:90973