Mouse Genome Informatics
hm1
    Dok1tm1Yyam/Dok1tm1Yyam
B6.129S4-Dok1tm1Yyam
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• percent body fat is reduced by more than 25% on both chow and high-fat diets
• body weight of mice are 10% lower than controls despite being similar in length
• mice weigh over 20% less than controls when fed a high fat diet for 12 weeks

adipose tissue
• mice have significantly less BAT than controls as measured by weight
• percent body fat is reduced by more than 25% on both chow and high-fat diets
• 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
• there are significantly less amounts of epididymal fat in these mice
• there are significantly less amounts of inguinal fat in these mice

homeostasis/metabolism
• 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
• mice fed a high-fat diet almost half the serum levels of leptin compared to wild-type mice
• mice have an increased oxygen consumption (normalized for body weight) when fed a high-fat diet
• mice have higher tolerance to glucose challenge after being fed a high-fat diet compared to controls
• 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
• mice fed a high-fat diet have higher serum levels of adiponectin


Mouse Genome Informatics
hm2
    Dok1tm1Yyam/Dok1tm1Yyam
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• stimulation with intact antibodies to IgM induced proliferation in mutant but not wild-type B cells
• IgM levels are lower in mutants without stimulation and after stimulation with a T dependent antigen

hematopoietic system
• stimulation with intact antibodies to IgM induced proliferation in mutant but not wild-type B cells
• IgM levels are lower in mutants without stimulation and after stimulation with a T dependent antigen


Mouse Genome Informatics
cx3
    Dok1tm1Yyam/Dok1tm1Yyam
Dok2tm1Yyam/Dok2tm1Yyam

B6.129-Dok1tm1Yyam Dok2tm1Yyam
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 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
• about half of the double homozygotes with myeloproliferative disease develop histiocytic sarcoma of macrophage origin

hematopoietic system
• hyperplasia of erythroblasts
• leukocyte numbers in the peripheral blood are significantly higher
• bone marrow and spleen have an increased ratio of immature granulocytic and/or monocytic precursors
• hyperplasia of myeloid precursors
• hyperplasia of megakaryocytes
• at about 1 year of age double homozygotes have enlarged spleens where immature and mature granulocytes/monocytes, erythroblasts, and atypical myeloid cells accumulate
• 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
• leukocyte numbers in the peripheral blood are significantly higher
• bone marrow and spleen have an increased ratio of immature granulocytic and/or monocytic precursors
• hyperplasia of myeloid precursors
• at about 1 year of age double homozygotes have enlarged spleens where immature and mature granulocytes/monocytes, erythroblasts, and atypical myeloid cells accumulate
• at 8 weeks of age bone marrow derived mast cells display increased proliferation in response to cytokines and attenuated apoptosis when deprived of cytokines

Mouse Models of Human Disease
OMIM IDRef(s)
Leukemia, Chronic Myeloid; CML 608232 J:95335


Mouse Genome Informatics
cx4
    Dok1tm1Yyam/Dok1tm1Yyam
Dok2tm1Yyam/Dok2tm1Yyam

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 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
• 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


Mouse Genome Informatics
cx5
    Dok1tm1Yyam/Dok1tm1Yyam
Dok2tm1Yyam/Dok2tm1Yyam
Dok3tm1Brs/Dok3tm1Brs

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• nearly half (15 of 33) of the mice died between 14?51 weeks after birth

tumorigenesis
• a markedly high incidence (24 of 41) of large cell tumors at 65 weeks of age
• 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
• abnormal Mac-2-positive macrophages in the lung
• bone marrow-derived macrophages at 10-12 weeks of age stimulated with M-CSF and GM-CSF, show an increased proliferative response

immune system
• abnormal Mac-2-positive macrophages in the lung
• bone marrow-derived macrophages at 10-12 weeks of age stimulated with M-CSF and GM-CSF, show an increased proliferative response


Mouse Genome Informatics
cx6
    Dok1tm1Yyam/Dok1tm1Yyam
Ppargtm1Laz/Ppargtm1Laz

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
N
• the characteristic resistance of Dok1tm1Yyam 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 homozygote background (J:133566)
• size of adipocytes is smaller compared to wild-type controls when a high-fat diet


Mouse Genome Informatics
cx7
    Dok1tm1Yyam/Dok1tm1Yyam
Tg(BCR/ABL1)5Hhi/0

involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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

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

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

endocrine/exocrine glands
• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Leukemia, Chronic Myeloid; CML 608232 J:95335


Mouse Genome Informatics
cx8
    Dok1tm1Yyam/Dok1tm1Yyam
Dok2tm1Yyam/Dok2tm1Yyam
Tg(BCR/ABL1)5Hhi/0

involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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

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

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

endocrine/exocrine glands
• enlarged thymus with massive infiltration of lymphoblasts seen at 4-5 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Leukemia, Chronic Myeloid; CML 608232 J:95335