All Phenotypes Dok1<tm1Yyam> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Dok1^tm1Yyam
targeted mutation 1, Yuji Yamanashi
MGI:3527415

Summary

8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dok1^tm1Yyam/Dok1^tm1Yyam	B6.129S4-Dok1^tm1Yyam	MGI:3804059
hm2	Dok1^tm1Yyam/Dok1^tm1Yyam	involves: 129S4/SvJae * C57BL/6	MGI:3574535
cx3	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam	B6.129-Dok1^tm1Yyam Dok2^tm1Yyam	MGI:3574536
cx4	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:4829895
cx5	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam Dok3^tm1Brs/Dok3^tm1Brs	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:4829896
cx6	Dok1^tm1Yyam/Dok1^tm1Yyam Pparg^tm1Laz/Pparg^tm1Laz	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:3804060
cx7	Dok1^tm1Yyam/Dok1^tm1Yyam Tg(Tec-BCR/ABL1)5Hhi/0	involves: C57BL/6	MGI:3574537
cx8	Dok1^tm1Yyam/Dok1^tm1Yyam Dok2^tm1Yyam/Dok2^tm1Yyam Tg(Tec-BCR/ABL1)5Hhi/0	involves: C57BL/6	MGI:3574538

Allelic Composition	Dok1^tm1Yyam/Dok1^tm1Yyam
Genetic Background	B6.129S4-Dok1^tm1Yyam

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dok1^tm1Yyam mutation (0 available); any Dok1 mutation (19 available)

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

growth/size/body

decreased body weight ( J:133566 )

• body weight of mice are 10% lower than controls despite being similar in length

decreased susceptibility to weight gain ( J:133566 )

• mice weigh over 20% less than controls when fed a high fat diet for 12 weeks

adipose tissue

decreased brown adipose tissue mass ( J:133566 )

• mice have significantly less BAT than controls as measured by weight

decreased fat cell size ( J:133566 )

• size of adipocytes is smaller compared to wild-type controls when both are fed a chow or a high-fat diet

• mouse embryonic fibroblasts are impaired in their ability to develop into adipocyte-like cells

decreased epididymal fat pad weight ( J:133566 )

• there are significantly less amounts of epididymal fat in these mice

decreased inguinal fat pad weight ( J:133566 )

• there are significantly less amounts of inguinal fat in these mice

decreased percent body fat/body weight ( J:133566 )

• percent body fat is reduced by more than 25% on both chow and high-fat diets

homeostasis/metabolism

decreased circulating insulin level ( J:133566 )

• insulin levels are two-thirds lower than control in mice fed a high fat diet

• plasma insulin levels are also two-thirds lower in these mice when given a bolus of glucose

decreased circulating leptin level ( J:133566 )

• mice fed a high-fat diet almost half the serum levels of leptin compared to wild-type mice

increased oxygen consumption ( J:133566 )

• mice have an increased oxygen consumption (normalized for body weight) when fed a high-fat diet

improved glucose tolerance ( J:133566 )

• mice have higher tolerance to glucose challenge after being fed a high-fat diet compared to controls

increased insulin sensitivity ( J:133566 )

• mice fed a high fat diet higher drops in blood sugar upon insulin challenge compared to wild-type mice fed the same diet

• mice have a lower score than controls on the homeostasis model assessment measure of insulin sensitivity

increased circulating adiponectin level ( J:133566 )

• mice fed a high-fat diet have higher serum levels of adiponectin

Allelic Composition	Dok1^tm1Yyam/Dok1^tm1Yyam
Genetic Background	involves: 129S4/SvJae * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dok1^tm1Yyam mutation (0 available); any Dok1 mutation (19 available)

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

immune system

increased B cell proliferation ( J:95641 )

• stimulation with intact antibodies to IgM induced proliferation in mutant but not wild-type B cells

decreased IgM level ( J:95641 )

• IgM levels are lower in mutants without stimulation and after stimulation with a T dependent antigen

hematopoietic system

increased B cell proliferation ( J:95641 )

• stimulation with intact antibodies to IgM induced proliferation in mutant but not wild-type B cells

decreased IgM level ( J:95641 )

• IgM levels are lower in mutants without stimulation and after stimulation with a T dependent antigen

cellular

increased B cell proliferation ( J:95641 )

• stimulation with intact antibodies to IgM induced proliferation in mutant but not wild-type B cells

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dok1^tm1Yyam mutation (0 available); any Dok1 mutation (19 available)
Dok2^tm1Yyam mutation (0 available); any Dok2 mutation (16 available)

♀	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

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

Find Mice

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

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

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

Find Mice

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

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

Allelic Composition	Dok1^tm1Yyam/Dok1^tm1Yyam Pparg^tm1Laz/Pparg^tm1Laz
Genetic Background	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dok1^tm1Yyam mutation (0 available); any Dok1 mutation (19 available)
Pparg^tm1Laz mutation (1 available); any Pparg mutation (41 available)

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

adipose tissue

adipose tissue phenotype ( J:133566 )

N	• the characteristic resistance of Dok1^tm1Yyam homozygotes to a high fat diet in terms of weight gain, adipose tissue growth, and rises in serum levels of leptin and insulin are normalized when mice are on a Pparg^tm1Laz homozygote background

abnormal fat cell morphology ( J:133566 )

• size of adipocytes is smaller compared to wild-type controls when a high-fat diet

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dok1^tm1Yyam mutation (0 available); any Dok1 mutation (19 available)
Tg(Tec-BCR/ABL1)5Hhi mutation (0 available)

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

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

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

Find Mice

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

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

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