Phenotypes associated with this allele

• Allele Symbol: Kmt2a⁺
• Allele Name: wild type
• Allele ID: MGI:2177860
• Summary: 16 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Kmt2a^tm1Clgr/Kmt2a^+	B6.129-Kmt2a^tm1Clgr	MGI:3691228
ht2	Kmt2a^tm2(MLLT3)Thr/Kmt2a^+	involves: 129P2/OlaHsd	MGI:4455033
ht3	Kmt2a^tm1Vss/Kmt2a^+	involves: 129P2/OlaHsd * C57BL/6	MGI:2177873
ht4	Kmt2a^tm1Saam/Kmt2a^+	involves: 129S1/Sv * C57BL/6	MGI:3814578
ht5	Kmt2a^tm1(AFF1)Ksy/Kmt2a^+	involves: 129S1/Sv * C57BL/6 * FVB	MGI:3712960
ht6	Kmt2a^tm1Sjk/Kmt2a^+	involves: 129S2/SvPas * C3H * C57BL/6	MGI:2177861
ht7	Kmt2a^tm1.1(Sh3gl1)Lcc/Kmt2a^+	involves: 129S/SvEv * C57BL/6	MGI:5559576
cn8	Kmt2a^tm1.1(Sh3gl1)Lcc/Kmt2a^+ Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6	MGI:5559577
cn9	Kmt2a^tm1Saam/Kmt2a^+ Tg(Mx1-cre)1Cgn/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:3814579
cn10	Kmt2a^tm1Thr/Kmt2a^+ Mllt1^tm1Thr/Mllt1^+ Tg(Lck-cre)1Thr/?	involves: 129S/SvEv	MGI:3720076
cn11	Kmt2a^tm1Thr/Kmt2a^+ Mllt3^tm2Thr/Mllt3^+ Tg(Lck-cre)1Thr/?	involves: 129S/SvEv	MGI:3720075
cn12	Lmo2^tm2(cre)Thr/Lmo2^+ Kmt2a^tm1Thr/Kmt2a^+ Mllt1^tm1Thr/Mllt1^+	involves: 129S/SvEv	MGI:2671953
cn13	Kmt2a^tm2Sjk/Kmt2a^+ Tg(Mx1-cre)1Cgn/0	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:3529267
cx14	Flt3^tm1Dgg/Flt3^tm1Dgg Kmt2a^tm1Clgr/Kmt2a^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445345
cx15	Flt3^tm1Dgg/Flt3^+ Kmt2a^tm1Clgr/Kmt2a^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445344
cx16	Kmt2a^tm1Tok/Kmt2a^+ Sf3b1^tm1Hko/Sf3b1^+	involves: C57BL/6	MGI:3574650

Genotype
MGI:3691228

ht1

• Allelic Composition: Kmt2a^tm1Clgr/Kmt2a⁺
• Genetic Background: B6.129-Kmt2a^tm1Clgr

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

Vertebral transformation is seen in Kmt2a^tm1Clgr/Mll1⁺ mice at 20 weeks of age

embryo

abnormal rostral-caudal axis patterning ( J:115001 )

• at E12.5 the boundary of Hoxa9 expression in the paraxial mesoderm is shifted ventrally

abnormal paraxial mesoderm morphology ( J:115001 )

skeleton

decreased rib number ( J:115001 )

• rudimentary or missing thirteenth rib in 70% of mice

vertebral transformation ( J:115001 )

thoracic vertebral transformation ( J:115001 )

• rudimentary or missing thirteenth rib indicates transformation of T13 to L1

sacral vertebral transformation ( J:115001 )

• S1 duplication in 63% of mice, indicative of S2 to S1 transformation

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:115001 )

• increase in the number of mixed colony forming units (GEMM-CFU) formed by cultured splenocytes

• cell from splenocyte colony forming assays form larger secondary colonies in replating assays and are able to form tertiary and quaternary colonies unlike wild-type cells however, in vivo cell counts in the bone marrow, spleen and blood are similar to wild type

• progenitor cells have a 2-fold increase in BrdU incorporation and a 50% increase in the amount of apoptosis

• progenitor cells are able to survive in culture for more than 4 months compared to less than 18 days for wild-type cells

abnormal myelopoiesis ( J:115001 )

• increase in the number of myeloid colony forming units (GM-CFU) formed by cultured splenocytes

increased erythroid progenitor cell number ( J:115001 )

• increase in the number of erythroid burst forming units (BFU-E) formed by cultured splenocytes

abnormal proerythroblast morphology ( J:115001 )

• 5- to 20-fold increase in the number of Ter119+ erythroid cells in the spleen

neoplasm

neoplasm ( J:115001 )

N • despite changes in hematopoiesis and Hoxa gene expression mice do not develop leukemia

immune system

abnormal myelopoiesis ( J:115001 )

• increase in the number of myeloid colony forming units (GM-CFU) formed by cultured splenocytes

Genotype
MGI:4455033

ht2

• Allelic Composition: Kmt2a^{tm2(MLLT3)Thr}/Kmt2a⁺
• Genetic Background: involves: 129P2/OlaHsd

neoplasm

increased leukemia incidence ( J:56340 )

• predominantly acute myeloid leukemia (AML) involving immature myeloblasts and extramedullary leukemia

• a minority of the observed leukemia is acute lymphoblastic leukemia (ALL)

• 50% of heterozygotes succumb to AML at 5 months of age

• almost all mice develop malignancy within 1 1/2 years

hematopoietic system

enlarged spleen ( J:56340 )

abnormal definitive hematopoiesis ( J:56340 )

• abnormal hematopoietic differentiation resulting in an accumulation of Mac-1/Gr-1 double-positive mature myeloid cells in the bone marrow preceded the onset of AML, as early as 6 days of age

immune system

enlarged spleen ( J:56340 )

liver/biliary system

enlarged liver ( J:56340 )

renal/urinary system

pale kidney ( J:56340 )

growth/size/body

enlarged liver ( J:56340 )

enlarged spleen ( J:56340 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:56340

Genotype
MGI:2177873

ht3

• Allelic Composition: Kmt2a^tm1Vss/Kmt2a⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

skeleton

abnormal rib development ( J:71498 )

• uni- or bi-lateral presence of rudimentary ribs on vertebra C7

• rib fusion to sternum

• absence of rib on vertebra T13

abnormal cervical vertebrae morphology ( J:71498 )

• broad and/or split neural arches

abnormal cervical atlas morphology ( J:71498 )

• fusions of C1 and C2

abnormal cervical axis morphology ( J:71498 )

• fusions of C1 and C2

cervical vertebral fusion ( J:71498 )

• fusions of C1 and C2

abnormal vertebral arch morphology ( J:71498 )

• broad and/or split neural arches in the cervical region

vertebral transformation ( J:71498 )

• various vertebral transformations

thoracic vertebral transformation ( J:71498 )

• vertebra T3 or t2 and T3 exhibit a spinous process

• transformations include T13 to L1

lumbar vertebral transformation ( J:71498 )

• vertebral transformations include L6 to S1

nervous system

abnormal cranial ganglia morphology ( J:71498 )

• reduced density of neurofilaments observed at E11.5

abnormal dorsal root ganglion morphology ( J:71498 )

• reduced density of neurofilaments observed at E11.5

• brachial plexus roots are less compacted

Genotype
MGI:3814578

ht4

• Allelic Composition: Kmt2a^tm1Saam/Kmt2a⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:140628 )

• born at slightly less than Mendelian frequency

Genotype
MGI:3712960

ht5

• Allelic Composition: Kmt2a^tm1(AFF1)Ksy/Kmt2a⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB

mortality/aging

premature death ( J:110241 )

• moribund mice (20 of 38 mice) were euthanized within a 22 month period of observation during which no wild-type mice died

hematopoietic system

enlarged spleen ( J:110241 )

• 7.3-fold in moribund mice

abnormal blood cell morphology/development ( J:110241 )

• immature cells are found in the blood

• moribund mice have blasts in their blood, exhibit benign lymphoid and myeloid hyperplasia in the spleen and bone marrow and exhibit myeloid disease

myeloid hyperplasia ( J:110241 )

• moribund mice exhibit myeloid hyperplasia in the spleen and bone marrow

increased leukocyte cell number ( J:110241 )

• 7.2x10³+/-1.2x10³/uL compared to 3.9x10³+/-1.0x10³/uL in wild-type mice

• counts are higher in moribund mice (10.4x10³+/-0.6x10³uL compared to 2.4x10³+/-0.2x10³uL in wild-type)

increased neutrophil cell number ( J:110241 )

increased monocyte cell number ( J:110241 )

• in moribund mice

abnormal lymphocyte morphology ( J:110241 )

• mice have the highest total number of lymphocytes

increased pro-B cell number ( J:110241 )

• pro-B cell colony forming units in vivo are significantly higher than in Mll1^tm2Thr homozygotes and wild-type mice

neoplasm

increased leukemia incidence ( J:110241 )

• myeloproliferative disorders (MPD)-like myeloid leukemia was detected in one mouse

increased B cell derived lymphoma incidence ( J:110241 )

• in moribund mice

increased malignant tumor incidence ( J:110241 )

• 20 of 38 mice develop hematologic malignancies with a mean time to development of 520 days

• lymphoid malignancy affected the spleen, lymph nodes and often liver, lung, intestine or kidney but not the blood

• one moribund mouse had a lymphoid malignancy in the spleen

increased spleen neoplasm incidence ( J:110241 )

• one moribund mouse had a lymphoid malignancy in the spleen

behavior/neurological

abnormal behavior ( J:110241 )

• in moribund mice

hunched posture ( J:110241 )

• in moribund mice

growth/size/body

abnormal facial morphology ( J:110241 )

• mice have blunt faces

short snout ( J:110241 )

big ears ( J:110241 )

decreased birth body size ( J:110241 )

• mice are small at birth

decreased body weight ( J:110241 )

• at 5 weeks, mice weigh 13.0g compared to wild-type mice that weigh 17.4g

enlarged spleen ( J:110241 )

• 7.3-fold in moribund mice

craniofacial

abnormal facial morphology ( J:110241 )

• mice have blunt faces

short snout ( J:110241 )

big ears ( J:110241 )

limbs/digits/tail

abnormal tail position or orientation ( J:110241 )

• high-set tail

immune system

enlarged spleen ( J:110241 )

• 7.3-fold in moribund mice

myeloid hyperplasia ( J:110241 )

• moribund mice exhibit myeloid hyperplasia in the spleen and bone marrow

increased leukocyte cell number ( J:110241 )

• 7.2x10³+/-1.2x10³/uL compared to 3.9x10³+/-1.0x10³/uL in wild-type mice

• counts are higher in moribund mice (10.4x10³+/-0.6x10³uL compared to 2.4x10³+/-0.2x10³uL in wild-type)

increased neutrophil cell number ( J:110241 )

increased monocyte cell number ( J:110241 )

• in moribund mice

abnormal lymphocyte morphology ( J:110241 )

• mice have the highest total number of lymphocytes

increased pro-B cell number ( J:110241 )

• pro-B cell colony forming units in vivo are significantly higher than in Mll1^tm2Thr homozygotes and wild-type mice

lymphoid hyperplasia ( J:110241 )

• in the spleen and bone marrow of moribund mice

• lymphoid tumors arise from follicular centers

hearing/vestibular/ear

big ears ( J:110241 )

integument

rough coat ( J:110241 )

• moribund mice have rough coat

Genotype
MGI:2177861

ht6

• Allelic Composition: Kmt2a^tm1Sjk/Kmt2a⁺
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6

reproductive system

reduced female fertility ( J:29958 )

♀

skeleton

abnormal sternum morphology ( J:29958 )

• 20 of 22 mice exhibit manubriosternebral abnormalities

• 17 of 22 mice exhibit xiphosternebral malformations

decreased rib number ( J:29958 )

• mice exhibit a complete loss or partial rib lose at T13

vertebral transformation ( J:29958 )

• mice exhibit C7/T13/L5 or C7/T12/L6 instead of C7/T13/L6 as in wild-type mice

thoracic vertebral transformation ( J:29958 )

• 18 of 22 mice exhibit T3 to T2 transformations

• 16 of 22 mice exhibit T2 to T1 transformations

• 8 of 22 mice exhibit T13 to L1 transformations

cervical vertebral transformation ( J:29958 )

• 14 of 22 mice exhibit C2 malformations compared to 4 of 29 mice

• 17 of 22 mice exhibit C7 to C6 transformations

lumbar vertebral transformation ( J:29958 )

• 19 of 22 mice exhibit L6 to S1 transformations

hematopoietic system

anemia ( J:29958 )

decreased erythrocyte cell number ( J:29958 )

decreased hemoglobin content ( J:29958 )

thrombocytopenia ( J:29958 )

decreased B cell number ( J:29958 )

growth/size/body

decreased birth body size ( J:29958 )

• mice are small at birth

postnatal growth retardation ( J:29958 )

immune system

decreased B cell number ( J:29958 )

Genotype
MGI:5559576

ht7

• Allelic Composition: Kmt2a^{tm1.1(Sh3gl1)Lcc}/Kmt2a⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:205605 )

• mice exhibit normal survival and phenotype

Genotype
MGI:5559577

cn8

• Allelic Composition: Kmt2a^{tm1.1(Sh3gl1)Lcc}/Kmt2a⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6

mortality/aging

premature death ( J:205605 )

• 50% survival at 6 months

immune system

enlarged spleen ( J:205605 )

• in some mice

myeloid hyperplasia ( J:205605 )

• increased immature myeloid cell population in the bone marrow, spleen and liver

enlarged lymph nodes ( J:205605 )

• in some mice

neoplasm

increased leukemia incidence ( J:205605 )

• acute myeloid leukemia after 12 months in some mice

• however, suppression of Prmt1 reduces leukemic cells

liver/biliary system

enlarged liver ( J:205605 )

• in some mice

hematopoietic system

enlarged spleen ( J:205605 )

• in some mice

myeloid hyperplasia ( J:205605 )

• increased immature myeloid cell population in the bone marrow, spleen and liver

growth/size/body

enlarged liver ( J:205605 )

• in some mice

enlarged spleen ( J:205605 )

• in some mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
leukemia		DOID:1240		J:205605

Genotype
MGI:3814579

cn9

• Allelic Composition: Kmt2a^tm1Saam/Kmt2a⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

neoplasm

increased leukemia incidence ( J:140628 )

• following pIpC treatment 14 of 22 mice developed acute leukemia

• median latency for leukemia development was 131 days

• infiltration of the bone marrow, spleen and liver with immature hematopoietic cells is seen in moribund mice

• mice may develop either acute myeloid leukemia or acute lymphoblastic leukemia

• gene expression profiles in mice with acute lymphoblastic leukemia recapitulate gene expression profiles seen in human acute lymphoid leukemia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute lymphoblastic leukemia		DOID:9952	OMIM:247640 OMIM:613065	J:140628
acute myeloid leukemia		DOID:9119	OMIM:601626	J:140628

Genotype
MGI:3720076

cn10

• Allelic Composition: Kmt2a^tm1Thr/Kmt2a⁺; Mllt1^tm1Thr/Mllt1⁺; Tg(Lck-cre)1Thr/?
• Genetic Background: involves: 129S/SvEv

neoplasm

neoplasm ( J:100794 )

N • no hematological malignancies are observed

Genotype
MGI:3720075

cn11

• Allelic Composition: Kmt2a^tm1Thr/Kmt2a⁺; Mllt3^tm2Thr/Mllt3⁺; Tg(Lck-cre)1Thr/?
• Genetic Background: involves: 129S/SvEv

neoplasm

increased hemolymphoid system tumor incidence ( J:100794 )

• 18 of 20 mice develop hematopoeitic neoplasm that are either T cell or myeloid in origin

• infiltration of malignant cells occurs in the liver, kidney, lungs and lymph nodes

increased T cell derived lymphoma incidence ( J:100794 )

• mice develop small T cell lymphomas

increased leukemia incidence ( J:100794 )

• mice have myelo-proliferative-like myeloid leukemia without circulating leukemic cells

hematopoietic system

increased T cell derived lymphoma incidence ( J:100794 )

• mice develop small T cell lymphomas

enlarged spleen ( J:100794 )

• splenomeglia is caused by a repopulation of the spleen with malignant cells

abnormal spleen red pulp morphology ( J:100794 )

• red and white pulp architecture is lost

abnormal spleen white pulp morphology ( J:100794 )

• red and white pulp architecture is lost

immune system

increased T cell derived lymphoma incidence ( J:100794 )

• mice develop small T cell lymphomas

enlarged spleen ( J:100794 )

• splenomeglia is caused by a repopulation of the spleen with malignant cells

abnormal spleen red pulp morphology ( J:100794 )

• red and white pulp architecture is lost

abnormal spleen white pulp morphology ( J:100794 )

• red and white pulp architecture is lost

growth/size/body

enlarged spleen ( J:100794 )

• splenomeglia is caused by a repopulation of the spleen with malignant cells

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:100794 )

• mice develop small T cell lymphomas

Genotype
MGI:2671953

cn12

• Allelic Composition: Lmo2^tm2(cre)Thr/Lmo2⁺; Kmt2a^tm1Thr/Kmt2a⁺; Mllt1^tm1Thr/Mllt1⁺
• Genetic Background: involves: 129S/SvEv

mortality/aging

premature death ( J:84518 )

• 100% of mutants either die or are sacrified due to ill health by 120 days of age

neoplasm

increased hemolymphoid system tumor incidence ( J:100794 )

• all mice develop hematological malignancies

• infiltration of malignant cells occurs in the liver, kidney, lungs and lymph nodes

increased leukemia incidence ( J:84518 , J:100794 )

• develop myeloid leukemias as early as 1.5 months of age (J:84518)

• leukemic cells invade the spleen and into peripheral organs such as liver and kidneys with perivascular deposits of tumor cells in liver and in between glomerili of kidney (J:84518)

• mice have myelo-proliferative-like myeloid leukemia (J:100794)

hematopoietic system

enlarged spleen ( J:84518 , J:100794 )

• splenomeglia is caused by a repopulation of the spleen with malignant cells (J:100794)

abnormal spleen red pulp morphology ( J:100794 )

• red and white pulp architecture is lost

abnormal spleen white pulp morphology ( J:100794 )

• red and white pulp architecture is lost

immune system

enlarged spleen ( J:84518 , J:100794 )

• splenomeglia is caused by a repopulation of the spleen with malignant cells (J:100794)

abnormal spleen red pulp morphology ( J:100794 )

• red and white pulp architecture is lost

abnormal spleen white pulp morphology ( J:100794 )

• red and white pulp architecture is lost

liver/biliary system

pale liver ( J:84518 )

renal/urinary system

pale kidney ( J:84518 )

growth/size/body

enlarged spleen ( J:84518 , J:100794 )

• splenomeglia is caused by a repopulation of the spleen with malignant cells (J:100794)

Genotype
MGI:3529267

cn13

• Allelic Composition: Kmt2a^tm2Sjk/Kmt2a⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

mortality/aging

increased mortality induced by gamma-irradiation ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants progress to fatal myeloid disease unlike controls

neoplasm

increased incidence of induced tumors ( J:95914 )

• within 7 months after pI-pC treated mutants were subjected to a sublethal dose of gamma-irradiation or an injection of ENU, 60% of gamma-irradiated and 73% of ENU-treated mutants succumbed to a spectrum of myeloproliferative diseases compared to none of the controls

• pI-pC treated gamma-irradiated mutants had leukemic infiltrates in the liver, lung, and lymph nodes

hematopoietic system

myeloid hyperplasia ( J:95914 )

• following pI-pC treatment, saw an increase in Mac-1+/Gr-1+ myeloid cells in bone marrow, indicating myeloid hyperplasia

• 3 weeks following pI-pC treatment, mutants had an average three-fold increase in granulocyte/macrophage progenitors (GMPs) and a three-fold reduction in the number of common lymphoid progenitors (CLPs) in the bone marrow

• enhanced self-renewal/proliferation of myeloid progenitors (hematopoietic stem cells (HSCs), GMPs and common myeloid progenitors (CMPs)) as indicated by their ability to generate colonies upon serial replating

anemia ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants developed anemia

abnormal bone marrow cell morphology/development ( J:95914 )

• following pI-pC treatment, gamma-irradiated mutant bone marrow contained pseudo-Gaucher cells, indicating high cell turnover

• following pI-pC treatment, gamma-irradiated and ENU treated mice had a significant increase in either Mac-1+/Gr-1-lo mature monocytes or Mac-1+/Gr-1+ immature myeloid cells and mature neutrophils and decreased B and T cells in the bone marrow

thrombocytopenia ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants developed thrombocytopenia

increased leukocyte cell number ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants had increased cell counts of mature monocytes and neutrophils

abnormal spleen morphology ( J:95914 )

• following pI-pC treatment, spleens from gamma-irradiated mutants showed extensive disruption of the splenic architecture by poorly differentiated myeloid cells

• following pI-pC treatment, gamma-irradiated and ENU treated mice had a significant increase in either Mac-1+/Gr-1-lo mature monocytes or Mac-1+/Gr-1+ immature myeloid cells and mature neutrophils and decreased B and T cells in the spleen

enlarged spleen ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants developed splenomegaly

increased spleen red pulp amount ( J:95914 )

• following pI-pC treatment, spleens from ENU treated mutants demonstrated marked expansion of red-pulp with megakaryoctyes, prominent erythropoiesis, and well-differentiated myelopoiesis

immune system

myeloid hyperplasia ( J:95914 )

• following pI-pC treatment, saw an increase in Mac-1+/Gr-1+ myeloid cells in bone marrow, indicating myeloid hyperplasia

• 3 weeks following pI-pC treatment, mutants had an average three-fold increase in granulocyte/macrophage progenitors (GMPs) and a three-fold reduction in the number of common lymphoid progenitors (CLPs) in the bone marrow

• enhanced self-renewal/proliferation of myeloid progenitors (hematopoietic stem cells (HSCs), GMPs and common myeloid progenitors (CMPs)) as indicated by their ability to generate colonies upon serial replating

increased leukocyte cell number ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants had increased cell counts of mature monocytes and neutrophils

abnormal spleen morphology ( J:95914 )

• following pI-pC treatment, spleens from gamma-irradiated mutants showed extensive disruption of the splenic architecture by poorly differentiated myeloid cells

• following pI-pC treatment, gamma-irradiated and ENU treated mice had a significant increase in either Mac-1+/Gr-1-lo mature monocytes or Mac-1+/Gr-1+ immature myeloid cells and mature neutrophils and decreased B and T cells in the spleen

enlarged spleen ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants developed splenomegaly

increased spleen red pulp amount ( J:95914 )

• following pI-pC treatment, spleens from ENU treated mutants demonstrated marked expansion of red-pulp with megakaryoctyes, prominent erythropoiesis, and well-differentiated myelopoiesis

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants progress to fatal myeloid disease unlike controls

growth/size/body

enlarged spleen ( J:95914 )

• following pI-pC treatment, gamma-irradiated or ENU treated mutants developed splenomegaly

Genotype
MGI:5445345

cx14

• Allelic Composition: Flt3^tm1Dgg/Flt3^tm1Dgg; Kmt2a^tm1Clgr/Kmt2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J

mortality/aging

premature death ( J:189096 )

• median survival is 19 weeks of age

neoplasm

increased leukemia incidence ( J:189096 )

• 89% develop acute myeloid leukemia

• 11% develop B-cell leukemia

• disease is more aggressive than in double heterozygous mutants

hematopoietic system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

immune system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

growth/size/body

enlarged spleen ( J:189096 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:189096

Genotype
MGI:5445344

cx15

• Allelic Composition: Flt3^tm1Dgg/Flt3⁺; Kmt2a^tm1Clgr/Kmt2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J

mortality/aging

premature death ( J:189096 )

• median survival of 49 weeks of age compared to 75-94 weeks of age for wild-type and single heterozygotes

neoplasm

increased leukemia incidence ( J:189096 )

• 100% penetrance of acute leukemia at a median age of 49 weeks

• 70% develop acute myeloid leukemia

• 12% develop unclassifiable acute leukemia

• 9% develop B-cell leukemia

• 9% develop biphenotypic leukemia

• loss of Flt3 heterozygosity is seen in leukemias

hematopoietic system

enlarged spleen ( J:189096 )

anemia ( J:189096 )

increased erythroblast number ( J:189096 )

• presence of more than or equal to 20% blasts in blood and blasts in nonhematopoietic organs, including liver and adrenal glands

thrombocytopenia ( J:189096 )

increased leukocyte cell number ( J:189096 )

• mutants develop leukocytosis

immune system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

• mutants develop leukocytosis

growth/size/body

enlarged spleen ( J:189096 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:189096

Genotype
MGI:3574650

cx16

• Allelic Composition: Kmt2a^tm1Tok/Kmt2a⁺; Sf3b1^tm1Hko/Sf3b1⁺
• Genetic Background: involves: C57BL/6

skeleton

skeleton phenotype ( J:96358 )

N • posterior vertebral transformations at the cervico-thoracic transitional zone caused by the Sf3b1 mutation were completely restored in double heterozygous mice