Phenotypes Associated with This Genotype

Genotype
MGI:3574536

• 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