Phenotypes associated with this allele

• Allele Symbol: Kmt2a^{tm2(MLLT3)Thr}
• Allele Name: targeted mutation 2, Terence H Rabbitts
• Allele ID: MGI:2671905
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kmt2a^tm2(MLLT3)Thr/Kmt2a^tm2(MLLT3)Thr	involves: 129P2/OlaHsd	MGI:2673833
hm2	Kmt2a^tm2(MLLT3)Thr/Kmt2a^tm2(MLLT3)Thr	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:3712961
ht3	Kmt2a^tm2(MLLT3)Thr/Kmt2a^+	involves: 129P2/OlaHsd	MGI:4455033

Genotype
MGI:2673833

hm1

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

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

mortality/aging

prenatal lethality ( J:56340 )

Genotype
MGI:3712961

hm2

• Allelic Composition: Kmt2a^{tm2(MLLT3)Thr}/Kmt2a^{tm2(MLLT3)Thr}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

hematopoietic system

abnormal blood cell morphology/development ( J:110241 )

• immature cells are found in the blood

abnormal definitive hematopoiesis ( J:110241 )

• bone marrow myeloid pro-B cell colony forming units in vivo are significantly higher than in wild-type and Mll1^tm1(AFF1)Ksy

• predominantly type I myeloid colonies are found

increased pro-B cell number ( J:110241 )

• pro-B cell colony forming units in vivo are significantly higher than in wild-type mice

increased leukocyte cell number ( J:110241 )

• 7.3x10³+/-1.3x10³/uL compared to 3.9x10³+/-1.0 x10³/uL in wild-type mice

• moribund mice have increased white blood cell counts (225.1 x10³+/-42.4 x10³uL compared to 2.4 x10³+/-0.2 x10³uL in wild-type mice)

increased neutrophil cell number ( J:110241 )

• 7.3x10³+/-1.3x10³/uL compared to 3.9x10³+/-1.0 x10³/uL in wild-type mice

• moribund mice have increased white blood cell counts (225.1 x10³+/-42.4 x10³uL compared to 2.4 x10³+/-0.2 x10³uL in wild-type mice)

neoplasm

increased hemolymphoid system tumor incidence ( J:110241 )

• 37 of 60 mice developed hematologic malignancies with a mean time to development of 220 days

• malignant cells exhibit a varying degree of differentiation from blast cells to cells with maturation into segmented neutrophils

increased leukemia incidence ( J:110241 )

• myeloproliferative disorders (MPD)-like myeloid leukemia is found in moribund mice

• leukemic infiltration of the spleen, bone marrow, liver, lymph nodes, and Peyer patches is observed

increased B cell derived lymphoma incidence ( J:110241 )

• in one moribund mice follicular B-cell lymphoma with myeloid proliferative disorder was observed

craniofacial

short face ( J:110241 )

• mice have short faces

pointed snout ( J:110241 )

big ears ( J:110241 )

• less severe than in Mll1^tm1(AFF1)Ksy homozygotes

growth/size/body

short face ( J:110241 )

• mice have short faces

pointed snout ( J:110241 )

big ears ( J:110241 )

• less severe than in Mll1^tm1(AFF1)Ksy homozygotes

decreased body size ( J:110241 )

• mice are small at birth

decreased body weight ( J:110241 )

• at 5 weeks, mice weigh 13.6g compared to wild-type mice that weigh 17.4g

immune system

increased pro-B cell number ( J:110241 )

• pro-B cell colony forming units in vivo are significantly higher than in wild-type mice

increased leukocyte cell number ( J:110241 )

• 7.3x10³+/-1.3x10³/uL compared to 3.9x10³+/-1.0 x10³/uL in wild-type mice

• moribund mice have increased white blood cell counts (225.1 x10³+/-42.4 x10³uL compared to 2.4 x10³+/-0.2 x10³uL in wild-type mice)

increased neutrophil cell number ( J:110241 )

• 7.3x10³+/-1.3x10³/uL compared to 3.9x10³+/-1.0 x10³/uL in wild-type mice

• moribund mice have increased white blood cell counts (225.1 x10³+/-42.4 x10³uL compared to 2.4 x10³+/-0.2 x10³uL in wild-type mice)

hearing/vestibular/ear

big ears ( J:110241 )

• less severe than in Mll1^tm1(AFF1)Ksy homozygotes

Genotype
MGI:4455033

ht3

• 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