Phenotypes associated with this allele

• Allele Symbol: Dok2^tm1Yyam
• Allele Name: targeted mutation 1, Yuji Yamanashi
• Allele ID: MGI:3527416
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam	B6.129-Dok1^tm1Yyam Dok2^tm1Yyam	MGI:3574536
cx2	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:4829895
cx3	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam Dok3^tm1Brs/Dok3^tm1Brs	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:4829896
cx4	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam Tg(Tec-BCR/ABL1)5Hhi/0	involves: C57BL/6	MGI:3574538
cx5	Dok2^tm1Yyam/Dok2^tm1Yyam Tg(Tec-BCR/ABL1)5Hhi/0	involves: C57BL/6	MGI:3574539

Genotype
MGI:3574536

cx1

• Allelic Composition: Dok1^tm1Yyam/Dok1^tm1Yyam; Dok2^tm1Yyam/Dok2^tm1Yyam
• Genetic Background: B6.129-Dok1^tm1Yyam Dok2^tm1Yyam

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

neoplasm

increased leukemia incidence ( J:95335 )

• double homozygotes develop myeloproliferative disease by about 1 year of age with atypical myeloid cells resembling myelomonocytic cells

• cellular infiltrations of granulocytes and lymphocytes are seen in several tissues

increased sarcoma incidence ( J:95335 )

• about half of the double homozygotes with myeloproliferative disease develop histiocytic sarcoma of macrophage origin

hematopoietic system

enlarged spleen ( J:95335 )

• at about 1 year of age double homozygotes have enlarged spleens where immature and mature granulocytes/monocytes, erythroblasts, and atypical myeloid cells accumulate

abnormal myelopoiesis ( J:95335 )

• bone marrow and spleen have an increased ratio of immature granulocytic and/or monocytic precursors

• hyperplasia of myeloid precursors

extramedullary hematopoiesis ( J:95335 )

increased megakaryocyte cell number ( J:95335 )

• hyperplasia of megakaryocytes

increased erythroblast number ( J:95335 )

• hyperplasia of erythroblasts

increased leukocyte cell number ( J:95335 )

• leukocyte numbers in the peripheral blood are significantly higher

increased neutrophil cell number ( J:95335 )

increased monocyte cell number ( J:95335 )

abnormal leukocyte physiology ( J:95335 )

• at 8 weeks of age bone marrow derived mast cells display increased proliferation in response to cytokines and attenuated apoptosis when deprived of cytokines

immune system

enlarged spleen ( J:95335 )

• at about 1 year of age double homozygotes have enlarged spleens where immature and mature granulocytes/monocytes, erythroblasts, and atypical myeloid cells accumulate

abnormal myelopoiesis ( J:95335 )

• bone marrow and spleen have an increased ratio of immature granulocytic and/or monocytic precursors

• hyperplasia of myeloid precursors

increased leukocyte cell number ( J:95335 )

• leukocyte numbers in the peripheral blood are significantly higher

increased neutrophil cell number ( J:95335 )

increased monocyte cell number ( J:95335 )

abnormal leukocyte physiology ( J:95335 )

• at 8 weeks of age bone marrow derived mast cells display increased proliferation in response to cytokines and attenuated apoptosis when deprived of cytokines

growth/size/body

enlarged spleen ( J:95335 )

• at about 1 year of age double homozygotes have enlarged spleens where immature and mature granulocytes/monocytes, erythroblasts, and atypical myeloid cells accumulate

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:95335

Genotype
MGI:4829895

cx2

• Allelic Composition: Dok1^tm1Yyam/Dok1^tm1Yyam; Dok2^tm1Yyam/Dok2^tm1Yyam
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

immune system

abnormal macrophage physiology ( J:163407 )

• bone marrow-derived macrophages at 10-12 weeks of age stimulated with M-CSF and GM-CSF, show an increased proliferative response compared to wild-type

hematopoietic system

abnormal macrophage physiology ( J:163407 )

• bone marrow-derived macrophages at 10-12 weeks of age stimulated with M-CSF and GM-CSF, show an increased proliferative response compared to wild-type

Genotype
MGI:4829896

cx3

• Allelic Composition: Dok1^tm1Yyam/Dok1^tm1Yyam; Dok2^tm1Yyam/Dok2^tm1Yyam; Dok3^tm1Brs/Dok3^tm1Brs
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

mortality/aging

premature death ( J:163407 )

• nearly half (15 of 33) of the mice died between 14?51 weeks after birth

neoplasm

increased tumor incidence ( J:163407 )

• a markedly high incidence (24 of 41) of large cell tumors at 65 weeks of age

increased histiocytic sarcoma incidence ( J:163407 )

• abnormal proliferative cells with histiocytic morphology and cell surface markers in the bone marrow, spleen, and/or liver

• the histiocytic sarcoma is highly invasive and transplantable

hematopoietic system

increased macrophage cell number ( J:163407 )

• abnormal Mac-2-positive macrophages in the lung

abnormal macrophage physiology ( J:163407 )

• bone marrow-derived macrophages at 10-12 weeks of age stimulated with M-CSF and GM-CSF, show an increased proliferative response

immune system

increased macrophage cell number ( J:163407 )

• abnormal Mac-2-positive macrophages in the lung

abnormal macrophage physiology ( J:163407 )

• bone marrow-derived macrophages at 10-12 weeks of age stimulated with M-CSF and GM-CSF, show an increased proliferative response

Genotype
MGI:3574538

cx4

• Allelic Composition: Dok1^tm1Yyam/Dok1^tm1Yyam; Dok2^tm1Yyam/Dok2^tm1Yyam; Tg(Tec-BCR/ABL1)5Hhi/0
• Genetic Background: involves: C57BL/6

mortality/aging

premature death ( J:95335 )

• mutants begin to die at 4-5 months of age with few surviving beyond 6-9 months of age unlike mice hemizygous for Tg(BCR/ABL1)5Hhi which survive until 1 year of age

neoplasm

increased leukemia incidence ( J:95335 )

• severe blastic transformation is seen at 4-5 months of age with tumor cells composed of double positive immature T lymphoblasts

immune system

enlarged thymus ( J:95335 )

• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

enlarged lymph nodes ( J:95335 )

• enlarged lymph node with massive infiltration of lymphoblasts seen at 4-5 months of age

hematopoietic system

enlarged thymus ( J:95335 )

• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

endocrine/exocrine glands

enlarged thymus ( J:95335 )

• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:95335

Genotype
MGI:3574539

cx5

• Allelic Composition: Dok2^tm1Yyam/Dok2^tm1Yyam; Tg(Tec-BCR/ABL1)5Hhi/0
• Genetic Background: involves: C57BL/6

mortality/aging

premature death ( J:95335 )

• mutants begin to die at 4-5 months of age with few surviving beyond 6-9 months of age unlike mice hemizygous for Tg(BCR/ABL1)5Hhi which survive until 1 year of age

neoplasm

increased leukemia incidence ( J:95335 )

• severe blastic transformation is seen at 4-5 months of age with tumor cells composed of double positive immature T lymphoblasts

immune system

enlarged thymus ( J:95335 )

• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

enlarged lymph nodes ( J:95335 )

• enlarged lymph node with massive infiltration of lymphoblasts seen at 4-5 months of age

hematopoietic system

enlarged thymus ( J:95335 )

• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

endocrine/exocrine glands

enlarged thymus ( J:95335 )

• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:95335