Phenotypes associated with this allele

• Allele Symbol: Dok1^tm1Ppp
• Allele Name: targeted mutation 1, Pier Paolo Pandolfi
• Allele ID: MGI:3527270
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dok1^tm1Ppp/Dok1^tm1Ppp	129S1/Sv-Dok1^tm1Ppp	MGI:3574540
cx2	Dok1^tm1Ppp/Dok1^tm1Ppp Dok2^tm1Ppp/Dok2^tm1Ppp	129S1/Sv-Dok1^tm1Ppp Dok2^tm1Ppp	MGI:3574543
cx3	Dok1^tm1Ppp/Dok1^tm1Ppp Dok2^tm1Ppp/Dok2^tm1Ppp Dok3^tm1Ppp/Dok3^tm1Ppp	129S1/Sv-Dok1^tm1Ppp Dok2^tm1Ppp Dok3^tm1Ppp	MGI:4443009
cx4	Dok1^tm1Ppp/Dok1^tm1Ppp Dok3^tm1Ppp/Dok3^tm1Ppp	129S1/Sv-Dok1^tm1Ppp Dok3^tm1Ppp	MGI:4443011
cx5	Dok1^tm1Ppp/Dok1^tm1Ppp Tg(Tec-BCR/ABL1)5Hhi/0	involves: 129S1/Sv	MGI:3574541
cx6	Dok1^tm1Ppp/Dok1^+ Tg(Tec-BCR/ABL1)5Hhi/0	involves: 129S1/Sv	MGI:3574545

Genotype
MGI:3574540

hm1

• Allelic Composition: Dok1^tm1Ppp/Dok1^tm1Ppp
• Genetic Background: 129S1/Sv-Dok1^tm1Ppp

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

immune system

abnormal T cell proliferation ( J:95640 )

• thymocytes display increased proliferation in response to ConA stimulation

neoplasm

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 38% of mice develop lung adenocarcinoma compared with 7% of wild-type mice

cellular

abnormal T cell proliferation ( J:95640 )

• thymocytes display increased proliferation in response to ConA stimulation

increased fibroblast proliferation ( J:95640 )

• primary embryonic fibroblasts display increased proliferation in response to PDGF stimulation

hematopoietic system

abnormal T cell proliferation ( J:95640 )

• thymocytes display increased proliferation in response to ConA stimulation

abnormal bone marrow cell morphology/development ( J:95640 )

• bone marrow derived mast cells display increased proliferation in response to low concentrations of cytokines; however, when deprived of cytokines mutant cells underwent apoptosis similar to wild-type cells

respiratory system

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 38% of mice develop lung adenocarcinoma compared with 7% of wild-type mice

Genotype
MGI:3574543

cx2

• Allelic Composition: Dok1^tm1Ppp/Dok1^tm1Ppp; Dok2^tm1Ppp/Dok2^tm1Ppp
• Genetic Background: 129S1/Sv-Dok1^tm1Ppp Dok2^tm1Ppp

neoplasm

increased leukemia incidence ( J:95334 )

• double homozygotes develop chronic myeloid leukemia-like myeloproliferative disease at 10-12 months of age

• this myeloproliferative disease is fully transplantable

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 32% of mice develop lung compared with 7% of wild-type mice adenocarcinoma

hematopoietic system

enlarged spleen ( J:95334 )

increased bone marrow cell number ( J:95334 )

• bone marrow hypercellularity and infiltration by myeloid cells that retain the ability to terminally differentiate are seen

increased leukocyte cell number ( J:95334 )

• a progressive increase in WBC numbers in the peripheral blood is seen after 4 months of age

• infiltration by myeloid cells that retain the ability to terminally differentiate is seen

increased neutrophil cell number ( J:95334 )

increased monocyte cell number ( J:95334 )

abnormal leukocyte physiology ( J:95334 )

• myeloid bone marrow cells display increased proliferation in response to growth factors and in the absence of growth factors and attenuated apoptosis when deprived of growth factors

immune system

enlarged spleen ( J:95334 )

increased leukocyte cell number ( J:95334 )

• a progressive increase in WBC numbers in the peripheral blood is seen after 4 months of age

• infiltration by myeloid cells that retain the ability to terminally differentiate is seen

increased neutrophil cell number ( J:95334 )

increased monocyte cell number ( J:95334 )

abnormal leukocyte physiology ( J:95334 )

• myeloid bone marrow cells display increased proliferation in response to growth factors and in the absence of growth factors and attenuated apoptosis when deprived of growth factors

respiratory system

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 32% of mice develop lung compared with 7% of wild-type mice adenocarcinoma

growth/size/body

enlarged spleen ( J:95334 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:95334

Genotype
MGI:4443009

cx3

• Allelic Composition: Dok1^tm1Ppp/Dok1^tm1Ppp; Dok2^tm1Ppp/Dok2^tm1Ppp; Dok3^tm1Ppp/Dok3^tm1Ppp
• Genetic Background: 129S1/Sv-Dok1^tm1Ppp Dok2^tm1Ppp Dok3^tm1Ppp

mortality/aging

premature death ( J:158011 )

• mice begin to die at around 1 year of age unlike wild-type mice

respiratory system

pulmonary hyperplasia ( J:158011 )

• mice exhibit an increase in the total number of lung cells compared with wild-type mice

• however, lung weight is normal

increased lung tumor incidence ( J:158011 )

• at 6 weeks, 30% of mice develop small lung tumors unlike wild-type mice

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 64% of mice develop lung adenocarcinoma compared with 7% of wild-type mice

increased bronchioalveolar stem cell number ( J:158011 )

• the number and percentages of bronchioalveolar stem cells are increased compared to in wild-type mice

abnormal pulmonary alveolus morphology ( J:158011 )

• at 12 weeks, mice exhibit alveolar hyperplasia with scattered bronchioaveolar stem cells unlike in wild-type mice

increased type II pneumocyte number ( J:158011 )

• the number and percentages of alveolar type 2 cells are increased compared to in wild-type mice

neoplasm

increased chronic myelocytic leukemia incidence ( J:158011 )

• at 20 months, mice exhibit an expansion of Mac-1+ and GR-1+ Mac-1+ cells compared with wild-type mice

• however, Mac-1+ and GR-1+ Mac-1+ cell numbers are normal at 3 months

increased lung tumor incidence ( J:158011 )

• at 6 weeks, 30% of mice develop small lung tumors unlike wild-type mice

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 64% of mice develop lung adenocarcinoma compared with 7% of wild-type mice

immune system

increased leukocyte cell number ( J:158011 )

• after 18 months

hematopoietic system

increased leukocyte cell number ( J:158011 )

• after 18 months

growth/size/body

pulmonary hyperplasia ( J:158011 )

• mice exhibit an increase in the total number of lung cells compared with wild-type mice

• however, lung weight is normal

Genotype
MGI:4443011

cx4

• Allelic Composition: Dok1^tm1Ppp/Dok1^tm1Ppp; Dok3^tm1Ppp/Dok3^tm1Ppp
• Genetic Background: 129S1/Sv-Dok1^tm1Ppp Dok3^tm1Ppp

neoplasm

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 51% of mice develop lung adenocarcinoma compared with 7% of wild-type mice

respiratory system

increased lung adenocarcinoma incidence ( J:158011 )

• at 11-25 months, 51% of mice develop lung adenocarcinoma compared with 7% of wild-type mice

Genotype
MGI:3574541

cx5

• Allelic Composition: Dok1^tm1Ppp/Dok1^tm1Ppp; Tg(Tec-BCR/ABL1)5Hhi/0
• Genetic Background: involves: 129S1/Sv

mortality/aging

premature death ( J:95334 )

• loss of Dok1 shortened lifespan to about 285 days from about 325 days in mice that are hemizygous for Tg(BCR/ABL1)5Hhi and wild-type for Dok1

neoplasm

increased leukemia incidence ( J:95334 )

• inactivation of Dok1 accelerated the onset of the chronic phase and the fatal blastic phase

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:95334

Genotype
MGI:3574545

cx6

• Allelic Composition: Dok1^tm1Ppp/Dok1⁺; Tg(Tec-BCR/ABL1)5Hhi/0
• Genetic Background: involves: 129S1/Sv

mortality/aging

premature death ( J:95334 )

• loss of Dok1 shortened lifespan to about 307 days from about 325 days in mice that are hemizygous for Tg(BCR/ABL1)5Hhi and wild-type for Dok1

neoplasm

increased leukemia incidence ( J:95334 )

• inactivation of Dok1 accelerated the onset of the chronic phase and the fatal blastic phase

• acceleration was not as severe as in homozygous null mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:95334