Phenotypes associated with this allele

• Allele Symbol: Tg(VAV1-cre)1Graf
• Allele Name: transgene insertion 1, Thomas Graf
• Allele ID: MGI:3765313
• Summary: 23 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(VAV1-cre)1Graf/0	involves: 129	MGI:5496430
cn2	Ccbe1^tm2.1Mlkn/Ccbe1^tm2.1Mlkn Tg(VAV1-cre)1Graf/0	involves: 129	MGI:5495739
cn3	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tg(VAV1-cre)1Graf/0	involves: 129 * C57BL/6 * SJL	MGI:5009037
cn4	Nbn^em7Jpt/Nbn^tm2Zqw Tg(VAV1-cre)1Graf/0	involves: 129P2/OlaHsd	MGI:6771693
cn5	Nbn^tm2Zqw/Nbn^tm2Zqw Tg(VAV1-cre)1Graf/0	involves: 129P2/OlaHsd	MGI:6771723
cn6	Cdkn2a^tm2Brn/Cdkn2a^tm2Brn Ezh1^tm1Sgon/Ezh1^tm1Sgon Tg(VAV1-cre)1Graf/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5474784
cn7	Rapgef2^tm1.1Hous/Rapgef2^tm1.1Hous Tg(VAV1-cre)1Graf/0	involves: 129S1/Sv	MGI:4839188
cn8	Lcp2^tm1Gak/Lcp2^tm2Gak Tg(VAV1-cre)1Graf/0 Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+	involves: 129S1/Sv * 129X1/SvJ	MGI:4843965
cn9	Ezh1^tm1Sgon/Ezh1^tm1Sgon Tg(VAV1-cre)1Graf/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5474783
cn10	Etv6^tm1(RUNX1)Haho/Etv6^+ Tg(VAV1-cre)1Graf/0	involves: 129S1/Sv * C57BL/6	MGI:4356083
cn11	Dot1l^tm1.1Saam/Dot1l^tm1.1Saam Tg(VAV1-cre)1Graf/0	involves: 129S1/Sv * C57BL/6	MGI:5468993
cn12	Runx1^tm3Spe/Runx1^tm3Spe Tg(VAV1-cre)1Graf/0	involves: 129S4/SvJae	MGI:3836437
cn13	Plvap^tm1.1Rvst/Plvap^tm1.1Rvst Tg(VAV1-cre)1Graf/0	involves: 129S4/SvJae * C57BL/6	MGI:5473523
cn14	Atm^tm2.1Fwa/Atm^tm2.1Fwa Tg(VAV1-cre)1Graf/0	involves: 129S6/SvEvTac	MGI:6771725
cn15	Ptpmt1^tm2.1Ckq/Ptpmt1^tm2.1Ckq Tg(VAV1-cre)1Graf/0	involves: 129S6/SvEvTac * C57BL/6J * SJL	MGI:5485993
cn16	Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(VAV1-cre)1Graf/0	involves: 129S/SvEv * C57BL/6	MGI:5141146
cn17	Tet2^tm1.1Iaai/Tet2^+ Tg(VAV1-cre)1Graf/0	involves: 129S/SvEv * C57BL/6	MGI:5141145
cn18	Ncstn^tm1.1Akli/Ncstn^tm1.1Akli Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(VAV1-cre)1Graf/0	involves: 129S/SvEv * C57BL/6	MGI:5496428
cn19	Asxl1^tm1.1Iaai/Asxl1^tm1.1Iaai Tg(VAV1-cre)1Graf/0	involves: 129S/SvEv * C57BL/6	MGI:5575662
cn20	Asxl1^tm1.1Iaai/Asxl1^tm1.1Iaai Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(VAV1-cre)1Graf/0	involves: 129S/SvEv * C57BL/6	MGI:5575663
cn21	Tg(VAV1-cre)1Graf/? Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/? Trip11^tm1.1Psmi/Trip11^tm1.2Psmi	involves: 129/Sv * C57BL/6	MGI:6154234
cn22	Ehmt2^tm1.1Cza/Ehmt2^tm1.1Cza Tg(VAV1-cre)1Graf/0	involves: C57BL/6 * SJL	MGI:4459648
cn23	Klf2^tm1Mlkn/Klf2^tm1Mlkn Tg(VAV1-cre)1Graf/0	Not Specified	MGI:3765433

Genotype
MGI:5496430

cn1

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129

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

mortality/aging

premature death ( J:196407 )

immune system

enlarged spleen ( J:196407 )

abnormal splenocyte physiology ( J:196407 )

• splenocytes transplanted into lethally irradiated recipients induce increased myeloid cell counts in peripheral blood compared with cells from control mice

• however, transplanted cells do not induce lethal myeloid leukemia

hematopoietic system

enlarged spleen ( J:196407 )

abnormal splenocyte physiology ( J:196407 )

• splenocytes transplanted into lethally irradiated recipients induce increased myeloid cell counts in peripheral blood compared with cells from control mice

• however, transplanted cells do not induce lethal myeloid leukemia

growth/size/body

enlarged spleen ( J:196407 )

Genotype
MGI:5495739

cn2

• Allelic Composition: Ccbe1^tm2.1Mlkn/Ccbe1^tm2.1Mlkn; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129

normal phenotype

no abnormal phenotype detected ( J:196696 )

• viable with no overt phenotypes and normal hematologic profiles

Genotype
MGI:5009037

cn3

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

premature death ( J:172442 )

• do not survive more than 20 weeks

hematopoietic system

abnormal definitive hematopoiesis ( J:172442 )

• significant reduction of the lymphoid-biased multipotential progenitor population (L-MPP)

• striking increase in the absolute numbers of both bone marrow and spleen granulocyte/monocyte progenitors cells

• decrease of the megakaryocyte?erythrocyte progenitor population

• progenitor cells display an increase in their self-renewal capacity

increased leukocyte cell number ( J:172442 )

• striking peripheral blood leukocytosis

increased monocyte cell number ( J:172442 )

• striking peripheral blood monocytosis

• increase in monocyte numbers in the bone marrow and liver

abnormal hematopoietic stem cell morphology ( J:172442 )

• de-repression of an extended myeloid-specific program in LSK cells

increased hematopoietic stem cell number ( J:172442 )

• increase in LSK numbers

abnormal spleen morphology ( J:172442 )

• expansion of the red pulp with diffuse infiltration by myeloid and monocytic cells

enlarged spleen ( J:172442 )

increased spleen red pulp amount ( J:172442 )

• expansion of the red pulp

neoplasm

increased leukemia incidence ( J:172442 )

• similarity to chronic myelomonocytic leukemia

immune system

increased leukocyte cell number ( J:172442 )

• striking peripheral blood leukocytosis

increased monocyte cell number ( J:172442 )

• striking peripheral blood monocytosis

• increase in monocyte numbers in the bone marrow and liver

abnormal spleen morphology ( J:172442 )

• expansion of the red pulp with diffuse infiltration by myeloid and monocytic cells

enlarged spleen ( J:172442 )

increased spleen red pulp amount ( J:172442 )

• expansion of the red pulp

growth/size/body

enlarged spleen ( J:172442 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic myeloid leukemia		DOID:8552	OMIM:608232	J:172442

Genotype
MGI:6771693

cn4

• Allelic Composition: Nbn^em7Jpt/Nbn^tm2Zqw; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:277750 )

• mice succumb to highly aggressive T cell malignancy with a median lifespan of 169 days

endocrine/exocrine glands

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

increased T cell derived lymphoma incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• lymphomas contain whole chromosome 15 duplications

hematopoietic system

increased T cell derived lymphoma incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• lymphomas contain whole chromosome 15 duplications

increased pro-B cell number ( J:277750 )

• pro-B cells (CD43+) are increased

impaired hematopoiesis ( J:277750 )

• hematopoiesis is severely impaired

decreased bone marrow cell number ( J:277750 )

• the cellularity of the bone marrow is decreased

thrombocytosis ( J:277750 )

• 2-fold elevation in platelets

decreased leukocyte cell number ( J:277750 )

• white blood cell counts are reduced in 6-to 8-week-old mice

decreased B cell number ( J:277750 )

• the percentage of peripheral B cells is decreased

• percentage of B lineage cells (B220+) is decreased by roughly 3-fold

• depletion of B cell lineage cells coincides with the onset of Ig gene assembly: whereas pro-B cells (CD43+) are increased, the levels of B220+ cell decrease beginning at the pre-B stage when Ig heavy chain rearrangement commences to the immature B cell stage (CD43-)

absent mature B cells ( J:277750 )

• IgM+ mature B cells are virtually undetectable

decreased myeloid cell number ( J:277750 )

• percentage of myeloid cells (Mac-1+ and Gr-1+) is decreased by roughly 3-fold

• however, levels of erythroid precursors (Ter119+) are unchanged

decreased erythrocyte cell number ( J:277750 )

• red blood cell numbers are reduced in 6-to 8-week-old mice

abnormal T cell morphology ( J:277750 )

• an increase in copy number of the MRE11 and CHK1 genes on chromosome 9 is detected in thymocytes as early as 4 weeks of age

• MYC amplification on chromosome 15 is detected in thymocytes at 4 weeks of age

increased CD8-positive, alpha-beta T cell number ( J:277750 )

• CD8+ population is elevated in the thymus at 6 weeks of age

decreased T cell number ( J:277750 )

• the percentage of peripheral T cells is decreased

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

immune system

increased T cell derived lymphoma incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• lymphomas contain whole chromosome 15 duplications

increased pro-B cell number ( J:277750 )

• pro-B cells (CD43+) are increased

decreased leukocyte cell number ( J:277750 )

• white blood cell counts are reduced in 6-to 8-week-old mice

decreased B cell number ( J:277750 )

• the percentage of peripheral B cells is decreased

• percentage of B lineage cells (B220+) is decreased by roughly 3-fold

• depletion of B cell lineage cells coincides with the onset of Ig gene assembly: whereas pro-B cells (CD43+) are increased, the levels of B220+ cell decrease beginning at the pre-B stage when Ig heavy chain rearrangement commences to the immature B cell stage (CD43-)

absent mature B cells ( J:277750 )

• IgM+ mature B cells are virtually undetectable

abnormal T cell morphology ( J:277750 )

• an increase in copy number of the MRE11 and CHK1 genes on chromosome 9 is detected in thymocytes as early as 4 weeks of age

• MYC amplification on chromosome 15 is detected in thymocytes at 4 weeks of age

increased CD8-positive, alpha-beta T cell number ( J:277750 )

• CD8+ population is elevated in the thymus at 6 weeks of age

decreased T cell number ( J:277750 )

• the percentage of peripheral T cells is decreased

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

neoplasm

increased T cell derived lymphoma incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• lymphomas contain whole chromosome 15 duplications

increased T cell acute lymphoblastic leukemia incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• tumors show the presence of multiple broad DNA copy number gains and losses, with recurrent copy number variation on chromosomes 9 and 15 and overexpression of MRE11 and CHK1

• leukemias contain activating mutation of NOTCH1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
T-cell acute lymphoblastic leukemia		DOID:5603		J:277750

Genotype
MGI:6771723

cn5

• Allelic Composition: Nbn^tm2Zqw/Nbn^tm2Zqw; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

postnatal lethality ( J:251434 , J:277750 )

• postnatal lethality due to lack of bone marrow development (J:251434)

• mice succumb at approximately 2 weeks of age to severe anemia (J:277750)

immune system

decreased leukocyte cell number ( J:251434 )

• large decrease in white blood cell count in 12-day-old mice

abnormal bone marrow development ( J:251434 )

• mice exhibit lack of bone marrow development

hematopoietic system

anemia ( J:277750 )

• severe anemia

decreased erythrocyte cell number ( J:251434 )

• large decrease in red blood cell count in 12-day-old mice

decreased leukocyte cell number ( J:251434 )

• large decrease in white blood cell count in 12-day-old mice

Genotype
MGI:5474784

cn6

• Allelic Composition: Cdkn2a^tm2Brn/Cdkn2a^tm2Brn; Ezh1^tm1Sgon/Ezh1^tm1Sgon; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:193722 )

N • rescue of hematopoiesis by increasing proliferation and alleviating senescence

Genotype
MGI:4839188

cn7

• Allelic Composition: Rapgef2^tm1.1Hous/Rapgef2^tm1.1Hous; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S1/Sv

hematopoietic system

hematopoietic system phenotype ( J:165879 )

N • mice exhibit normal adult hematopoiesis

immune system

immune system phenotype ( J:165879 )

N • mice exhibit normal B cell and T cell development

Genotype
MGI:4843965

cn8

• Allelic Composition: Lcp2^tm1Gak/Lcp2^tm2Gak; Tg(VAV1-cre)1Graf/0; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

immune system

abnormal lymphatic vessel morphology ( J:162815 )

• at E14.5, mice exhibit blood-filled cutaneous lymphatics unlike in wild-type mice

• neonates exhibit blood-filled mesenteric lymphatics unlike in wild-type mice

digestive/alimentary system

intestinal edema ( J:162815 )

homeostasis/metabolism

intestinal edema ( J:162815 )

Genotype
MGI:5474783

cn9

• Allelic Composition: Ezh1^tm1Sgon/Ezh1^tm1Sgon; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:193722 )

N • mice exhibit normal numbers of myeloid progenitors and colony-forming cells

N • mice exhibit normal fetal hematopoiesis

decreased pro-B cell number ( J:193722 )

decreased bone marrow cell number ( J:193722 )

• 2-fold reduction in bone marrow cellularity with 2-fold fewer side population cells

abnormal common lymphocyte progenitor cell morphology ( J:193722 )

• reduced mature lymphoid progenitor pools

decreased B cell number ( J:193722 )

• in the peripheral blood

decreased immature B cell number ( J:193722 )

decreased hematopoietic stem cell number ( J:193722 )

• long term, short term and multipotent progenitors with 2-fold fewer side population cells

abnormal myeloid leukocyte morphology ( J:193722 )

• slight decrease in the peripheral blood

decreased spleen red pulp amount ( J:193722 )

small spleen ( J:193722 )

absent spleen germinal center ( J:193722 )

decreased spleen white pulp amount ( J:193722 )

abnormal bone marrow cell physiology ( J:193722 )

• bone marrow failure is hematopoietic cell autonomous

abnormal hematopoietic stem cell physiology ( J:193722 )

• long term and short term hematopoietic stem cells/ multipotent progenitors exhibit reduced cell cycling and senescence compared with control cells

• hematopoietic stem cells (HSCs) are unable to engraft tertiary recipients

• in transplant experiments, HSCs exhibit defective homing in the bone marrow

• bone marrow failure is hematopoietic cell autonomous

cellular

early cellular replicative senescence ( J:193722 )

• in hematopoietic stem cell

immune system

decreased pro-B cell number ( J:193722 )

decreased B cell number ( J:193722 )

• in the peripheral blood

decreased immature B cell number ( J:193722 )

abnormal myeloid leukocyte morphology ( J:193722 )

• slight decrease in the peripheral blood

decreased spleen red pulp amount ( J:193722 )

small spleen ( J:193722 )

absent spleen germinal center ( J:193722 )

decreased spleen white pulp amount ( J:193722 )

lymphoid hypoplasia ( J:193722 )

• in the spleen

Genotype
MGI:4356083

cn10

• Allelic Composition: Etv6^{tm1(RUNX1)Haho}/Etv6⁺; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S1/Sv * C57BL/6

hematopoietic system

decreased pro-B cell number ( J:151639 )

• mildly

arrested B cell differentiation ( J:151639 )

• transplantation of fetal liver cells into Rag null mice exhibit a decrease in early B cells confirms a specific adult block in B cell development

abnormal myeloblast morphology/development ( J:151639 )

• myeloid progenitors are increased compared to in untreated mice

decreased B cell number ( J:151639 )

• early be cells is almost completely depleted

decreased pre-B cell number ( J:151639 )

• mildly

increased hematopoietic stem cell number ( J:151639 )

immune system

decreased pro-B cell number ( J:151639 )

• mildly

arrested B cell differentiation ( J:151639 )

• transplantation of fetal liver cells into Rag null mice exhibit a decrease in early B cells confirms a specific adult block in B cell development

decreased B cell number ( J:151639 )

• early be cells is almost completely depleted

decreased pre-B cell number ( J:151639 )

• mildly

Genotype
MGI:5468993

cn11

• Allelic Composition: Dot1l^tm1.1Saam/Dot1l^tm1.1Saam; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S1/Sv * C57BL/6

hematopoietic system

abnormal definitive hematopoiesis ( J:193161 )

• moderate to severe reduction in hematopoietic stem cells, granulocyte-macrophage progenitors and common myeloid progenitors with less of an affect on megakaryocyte/erythroid progenitors

decreased common myeloid progenitor cell number ( J:193161 )

• moderately to severely

abnormal leukopoiesis ( J:193161 )

• moderately to severely reduction in granulocyte-macrophage progenitors

anemia ( J:193161 )

• varying degrees in young mice

impaired hematopoiesis ( J:193161 )

• but not absent

decreased bone marrow cell number ( J:193161 )

decreased neutrophil cell number ( J:193161 )

• mild to moderate in young mice

decreased lymphocyte cell number ( J:193161 )

• mild to moderate in young mice

decreased hematopoietic stem cell number ( J:193161 )

• moderately to severely

immune system

abnormal leukopoiesis ( J:193161 )

• moderately to severely reduction in granulocyte-macrophage progenitors

decreased neutrophil cell number ( J:193161 )

• mild to moderate in young mice

decreased lymphocyte cell number ( J:193161 )

• mild to moderate in young mice

Genotype
MGI:3836437

cn12

• Allelic Composition: Runx1^tm3Spe/Runx1^tm3Spe; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S4/SvJae

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:145700 )

• increased numbers of CFU-G and CFU-GEMM can be derived from E15.5 fetal livers compared to controls

increased granulocyte number ( J:145700 )

• numbers are increased almost 3-fold

abnormal platelet morphology ( J:145700 )

• increased numbers of CFU-G and CFU-GEMM can be derived from E15.5 fetal livers compared to controls

decreased lymphocyte cell number ( J:145700 )

• lymphocyte numbers are reduced by about a third

decreased thymocyte number ( J:145700 )

• there is about a 10-fold reduction in thymocyte number

decreased double-positive T cell number ( J:145700 )

• numbers in the thymus are decreased by half

decreased B cell number ( J:145700 )

• B cell numbers are greatly reduced

increased monocyte cell number ( J:145700 )

• numbers are increased over 2-fold

increased hematopoietic stem cell number ( J:145700 )

• lin^- Sca-1⁺ kit⁺ cell numbers in the bone marrow are increased about 5 fold

• increased numbers of CFU-C can be derived from E15.5 fetal livers compared to controls

• the vast majority of the CFUs have both alleles of the Runx1 gene deleted

immune system

increased granulocyte number ( J:145700 )

• numbers are increased almost 3-fold

decreased lymphocyte cell number ( J:145700 )

• lymphocyte numbers are reduced by about a third

decreased thymocyte number ( J:145700 )

• there is about a 10-fold reduction in thymocyte number

decreased double-positive T cell number ( J:145700 )

• numbers in the thymus are decreased by half

decreased B cell number ( J:145700 )

• B cell numbers are greatly reduced

increased monocyte cell number ( J:145700 )

• numbers are increased over 2-fold

endocrine/exocrine glands

decreased thymocyte number ( J:145700 )

• there is about a 10-fold reduction in thymocyte number

Genotype
MGI:5473523

cn13

• Allelic Composition: Plvap^tm1.1Rvst/Plvap^tm1.1Rvst; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

mortality/aging ( J:191046 )

N • no mortality is seen

cardiovascular system

cardiovascular system phenotype ( J:191046 )

N • diaphragms in endothelial fenestrae, transendothelial channels, and caveolae in pancreas, intestine, kidney, lung and adrenals are similar to controls

Genotype
MGI:6771725

cn14

• Allelic Composition: Atm^tm2.1Fwa/Atm^tm2.1Fwa; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S6/SvEvTac

endocrine/exocrine glands

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

increased T cell derived lymphoma incidence ( J:277750 )

• mice develop thymic lymphomas; tumors exhibit a relatively immature phenotype (CD3low CD4+ CD8+)

hematopoietic system

increased T cell derived lymphoma incidence ( J:277750 )

• mice develop thymic lymphomas; tumors exhibit a relatively immature phenotype (CD3low CD4+ CD8+)

decreased B cell number ( J:277750 )

• the percentage of peripheral B cells is decreased

decreased T cell number ( J:277750 )

• the percentage of peripheral T cells is decreased

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

immune system

increased T cell derived lymphoma incidence ( J:277750 )

• mice develop thymic lymphomas; tumors exhibit a relatively immature phenotype (CD3low CD4+ CD8+)

decreased B cell number ( J:277750 )

• the percentage of peripheral B cells is decreased

decreased T cell number ( J:277750 )

• the percentage of peripheral T cells is decreased

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

neoplasm

increased T cell derived lymphoma incidence ( J:277750 )

• mice develop thymic lymphomas; tumors exhibit a relatively immature phenotype (CD3low CD4+ CD8+)

Genotype
MGI:5485993

cn15

• Allelic Composition: Ptpmt1^tm2.1Ckq/Ptpmt1^tm2.1Ckq; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:194929 )

• within 5 to 9 days of birth

• however, mice can be rescued by transplantation of wild-type bone marrow cells

hematopoietic system

small thymus ( J:194929 )

anemia ( J:194929 )

• severe

impaired hematopoiesis ( J:194929 )

• neonatal

decreased bone marrow cell number ( J:194929 )

• 75-fold by P5

pancytopenia ( J:194929 )

increased hematopoietic stem cell number ( J:194929 )

• 30-fold; develops gradually

small spleen ( J:194929 )

immune system

small thymus ( J:194929 )

small spleen ( J:194929 )

endocrine/exocrine glands

small thymus ( J:194929 )

Genotype
MGI:5141146

cn16

• Allelic Composition: Tet2^tm1.1Iaai/Tet2^tm1.1Iaai; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

enlarged spleen ( J:174053 )

• at 20 weeks

increased spleen weight ( J:174053 )

• at 20 weeks

abnormal common myeloid progenitor cell morphology ( J:174053 )

• increased myeloid progenitors in the spleen

extramedullary hematopoiesis ( J:174053 )

• in the spleen

increased hematopoietic cell number ( J:174053 )

• in the spleen

myeloid hyperplasia ( J:174053 )

• mice exhibit an increase in the GMP population (including monocyte and granulocyte progenitors) compared with wild-type mice

increased leukocyte cell number ( J:174053 )

• at 20 weeks, progressive in the peripheral blood

increased monocyte cell number ( J:174053 )

• at 20 weeks

abnormal myeloid leukocyte morphology ( J:174053 )

• at 20 weeks, bone marrow and peripheral lymphoid tissue exhibit myeloid dysplasia (including blasts, promyelocytes, myelocytes, or metamyelocytes) unlike in wild-type mice

abnormal hematopoietic stem cell physiology ( J:174053 )

• hematopoietic progenitors exhibit increased serial replating capacity compared with control cells

neoplasm

increased chronic myelocytic leukemia incidence ( J:174053 )

• at 20 weeks, mice exhibit chronic myelomonocytic leukemia (CMML)-like phenotype unlike wild-type mice

immune system

enlarged spleen ( J:174053 )

• at 20 weeks

increased spleen weight ( J:174053 )

• at 20 weeks

myeloid hyperplasia ( J:174053 )

• mice exhibit an increase in the GMP population (including monocyte and granulocyte progenitors) compared with wild-type mice

increased leukocyte cell number ( J:174053 )

• at 20 weeks, progressive in the peripheral blood

abnormal myeloid leukocyte morphology ( J:174053 )

• at 20 weeks, bone marrow and peripheral lymphoid tissue exhibit myeloid dysplasia (including blasts, promyelocytes, myelocytes, or metamyelocytes) unlike in wild-type mice

increased monocyte cell number ( J:174053 )

• at 20 weeks

growth/size/body

enlarged spleen ( J:174053 )

• at 20 weeks

increased spleen weight ( J:174053 )

• at 20 weeks

Genotype
MGI:5141145

cn17

• Allelic Composition: Tet2^tm1.1Iaai/Tet2⁺; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

extramedullary hematopoiesis ( J:174053 )

increased hematopoietic cell number ( J:174053 )

• in the spleen

increased leukocyte cell number ( J:174053 )

• progressive in the peripheral blood

increased monocyte cell number ( J:174053 )

• in the peripheral blood

abnormal hematopoietic stem cell physiology ( J:174053 )

• hematopoietic progenitors exhibit increased serial replating capacity compared with control cells

immune system

increased leukocyte cell number ( J:174053 )

• progressive in the peripheral blood

increased monocyte cell number ( J:174053 )

• in the peripheral blood

Genotype
MGI:5496428

cn18

• Allelic Composition: Ncstn^tm1.1Akli/Ncstn^tm1.1Akli; Tet2^tm1.1Iaai/Tet2^tm1.1Iaai; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

mortality/aging

premature death ( J:196407 )

• mice die at 26 weeks

immune system

enlarged spleen ( J:196407 )

• with massive infiltration of differentiated and blast-like myeloid cells

myeloid hyperplasia ( J:196407 )

• increased circulating blast-like cells at 7 weeks after birth

• massive infiltration of differentiated and blast-like myeloid cells in the spleen

increased leukocyte cell number ( J:196407 )

• with an increase in absolute myelomonocytic and blast-like cells 7 weeks after birth

neoplasm

abnormal tumor pathology ( J:196407 )

• spleen tumor cells transplanted into lethally irradiated recipients induce increased myeloid cell counts in peripheral blood and lethality compared with cells from control mice

increased leukemia incidence ( J:196407 )

• massive infiltration of differentiated and blast-like myeloid cells in the spleen

hematopoietic system

enlarged spleen ( J:196407 )

• with massive infiltration of differentiated and blast-like myeloid cells

abnormal common myeloid progenitor cell morphology ( J:196407 )

• enlarged granulocyte-macrophage progenitor (GMP) compartment

myeloid hyperplasia ( J:196407 )

• increased circulating blast-like cells at 7 weeks after birth

• massive infiltration of differentiated and blast-like myeloid cells in the spleen

increased leukocyte cell number ( J:196407 )

• with an increase in absolute myelomonocytic and blast-like cells 7 weeks after birth

growth/size/body

enlarged spleen ( J:196407 )

• with massive infiltration of differentiated and blast-like myeloid cells

Genotype
MGI:5575662

cn19

• Allelic Composition: Asxl1^tm1.1Iaai/Asxl1^tm1.1Iaai; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

abnormal definitive hematopoiesis ( J:208092 )

• increase in the absolute number of immunophenotypically defined hematopoietic stem cells at 6 weeks of age, however a decrease in serial plating in vitro is seen, indicating a defect in self-renewal of hematopoietic stem cells

• transplantation experiments show that hematopoietic stem cells show impaired self-renewal

• transplantation of whole bone marrow from mutants into lethally irradiated recipients results in a lethal hematopoietic disorder

abnormal myelopoiesis ( J:208092 )

• 6 month old mice show dysplasia of circulating myeloid cells

• analysis of sorted myeloid progenitor cells from 6 week old mice shows a decrease in colony output of sorted common myeloid progenitors, granulocyte/macrophage progenitors, and megakaryocyte/erythroid progenitors

anemia ( J:208092 )

• develop progressive anemia that is most apparent at 6-12 months of age

decreased bone marrow cell number ( J:208092 )

• mice develop progressive bone marrow hypocellularity beginning at 6 weeks of age that is still seen at 24 weeks of age

increased erythroid progenitor cell number ( J:208092 )

• 1.4- to 2-fold increase in CD71+/Ter119- erythoroid precursor cells in the bone marrow and spleen, indicating impaired erythroid differentiation

decreased hemoglobin content ( J:208092 )

• hemoglobin is reduced at between 6 and 12 months of age, but not in mice younger than 6 months

increased nucleated erythrocyte cell number ( J:208092 )

• 6 month old mice show frequent circulating nucleated red cells

decreased leukocyte cell number ( J:208092 )

• develop progressive leukopenia that is most apparent at 6-12 months of age

• leukopenia is predominately as a result of decreased B220+ mature B cells, CD11b+Gr1+ neutrophils, and CD11b+Gr1- monocytes

decreased neutrophil cell number ( J:208092 )

• decrease in CD11b+Gr1+ neutrophils

decreased mature B cell number ( J:208092 )

• decrease in B220+ mature B cells

decreased monocyte cell number ( J:208092 )

• decrease in CD11b+Gr1- monocytes

abnormal hematopoietic stem cell morphology ( J:208092 )

• mice show increased apoptosis and altered cell cycle distribution (decrease in S-phase) of hematopoietic stem cells

increased hematopoietic stem cell number ( J:208092 )

• mice show an increase in the frequency and total number of hematopoietic stem cells

decreased splenocyte number ( J:208092 )

• mice develop progressive splenic hypocellularity beginning at 6 weeks of age that is still seen at 24 weeks of age

immune system

abnormal myelopoiesis ( J:208092 )

• 6 month old mice show dysplasia of circulating myeloid cells

• analysis of sorted myeloid progenitor cells from 6 week old mice shows a decrease in colony output of sorted common myeloid progenitors, granulocyte/macrophage progenitors, and megakaryocyte/erythroid progenitors

decreased leukocyte cell number ( J:208092 )

• develop progressive leukopenia that is most apparent at 6-12 months of age

• leukopenia is predominately as a result of decreased B220+ mature B cells, CD11b+Gr1+ neutrophils, and CD11b+Gr1- monocytes

decreased neutrophil cell number ( J:208092 )

• decrease in CD11b+Gr1+ neutrophils

decreased mature B cell number ( J:208092 )

• decrease in B220+ mature B cells

decreased monocyte cell number ( J:208092 )

• decrease in CD11b+Gr1- monocytes

decreased splenocyte number ( J:208092 )

• mice develop progressive splenic hypocellularity beginning at 6 weeks of age that is still seen at 24 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:208092

Genotype
MGI:5575663

cn20

• Allelic Composition: Asxl1^tm1.1Iaai/Asxl1^tm1.1Iaai; Tet2^tm1.1Iaai/Tet2^tm1.1Iaai; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129S/SvEv * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:208092 )

N • colony assays of whole bone marrow cells show restored serial-replating capacity of cells and competitive transplantation experiments show restoration of the self-renewal defect seen in single conditional Asxl1 mutants

Genotype
MGI:6154234

cn21

• Allelic Composition: Tg(VAV1-cre)1Graf/?; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/?; Trip11^tm1.1Psmi/Trip11^tm1.2Psmi
• Genetic Background: involves: 129/Sv * C57BL/6

immune system

immune system phenotype ( J:253969 )

N • normal IgG secretion

skeleton

skeleton phenotype ( J:253969 )

N • these mice, which have a hemotopoietic conditional null of a gene involved in vesicle transport, develop normally with both endochondral and intramembranous bones being of normal size and mineralization, the osteoblasts have normal Golgi apparatus stack structure and no swelling of the endoplasmic, the humeri at birth show normal trabeculae, cortical bone, and bone marrow, and micro CT measurements at 6 weeks of age are normal, so osteoblast and osteoclast function appear normal

Genotype
MGI:4459648

cn22

• Allelic Composition: Ehmt2^tm1.1Cza/Ehmt2^tm1.1Cza; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: C57BL/6 * SJL

Goblet cell hyperplasia in response to T. muris infection in Ehmt2^tm1.1Cza/Ehmt2^tm1.1Cza Tg(VAV1-cre)1Graf/0 mice and treatment with an anti-IFN-gamma antibody fails to recover the hyperplasia

immune system

increased interferon-gamma secretion ( J:160938 )

decreased interleukin-13 secretion ( J:160938 )

• in neutral or Th2 polarizing culture conditions

increased interleukin-17 secretion ( J:160938 )

• under neutral and Th2 conditions increased IL17A

decreased interleukin-4 secretion ( J:160938 )

• in neutral culture conditions

decreased interleukin-5 secretion ( J:160938 )

• in neutral or Th2 polarizing culture conditions

increased susceptibility to parasitic infection ( J:160938 )

• susceptible to T. muris infection, failing to clear parasites from the GI tract

digestive/alimentary system

abnormal intestinal goblet cell morphology ( J:160938 )

• hyperplasia in response to T. muris infection

cellular

abnormal intestinal goblet cell morphology ( J:160938 )

• hyperplasia in response to T. muris infection

Genotype
MGI:3765433

cn23

• Allelic Composition: Klf2^tm1Mlkn/Klf2^tm1Mlkn; Tg(VAV1-cre)1Graf/0
• Genetic Background: Not Specified

immune system

absent T cells ( J:127228 )

• mice lack T cells in the peripheral blood

hematopoietic system

absent T cells ( J:127228 )

• mice lack T cells in the peripheral blood